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Archive for February, 2012

On the Horizon: A Real Cure for All Cancers?

Introduction

The world of medicine is changing and nanotechnology is leading the way. The future of cancer diagnosis and treatment does indeed look bright.

Where cancer research and treatment is concerned there is clearly a need to develop new innovative diagnostic and therapeutic methods. During the last 10 years tremendous progress has been made in the development of new molecular imaging probes and therapeutic agents targeting cancer. One such field that has contributed greatly in the area of diagnostic and therapeutic methods is the field of nanotechnology (technology for use on the atomic or molecular level.)  For example, there are now nanoparticle enabled technologies that do a better job of detecting and treating cancer than ever before. There appears to be three goals of these newer technologies:

(1)   Early detection of the disease

(2)   Enhance the ability to monitor therapeutic response, and

(3)   Enable the ability to target delivery of therapeutic agents, like cancer killing drugs.

There are other uses of nanotechnology, but the purpose of this Blog is to focus on the use of nanotechnology in the treatment of the devastating disease of cancer. In my grandmother’s day a diagnosis of cancer was a death sentence. From personal experience, I know that in today’s world that is not necessarily true.

 

Connections

In 2004 I lost a kidney to kidney cancer. I nevertheless was one of the lucky ones because I am a kidney cancer survivor for 8 years now. Consequently, I have a personal stake in finding a cure for cancer (and reoccurrences of same). I was astonished recently (and got goose bumps all over) when I read about a 17- year old high school senior from Cupertino, California who may have found a way to cure cancer.

Her name is Angela Zhang. She has received a $100,000 scholarship for her science school project because of the extraordinary nature of what she was trying to put forth—a comprehensive self-contained way to use nanoparticles to isolate and treat all cancer tumors, while leaving healthy tissue and cells alone. The $100,000 Zhang earned comes with the first prize award in the Siemens Competition in Math, Science & Technology.

In my opinion, Angela Zhang is not necessarily a super-genius. But she is a very bright, precocious, and persevering young person who demonstrated an uncanny ability to logically synthesize existing research data, and ideas from specialized scientific fields. In this case, she researched the field of nanotechnology, and more specifically she emphasized synthesizing information from the sub-field of medical nanotechnology.

But, of course, what she did wasn’t only a clever assimilation of research ideas from the scientific literature. There was that hands-on 1,000 hours creating the nanoparticle, and figuring out how to integrate a drug delivery system at the micron level that could be closely monitored for its effects. And, she achieved a very important aspect of cancer treatment—delivering a cancer drug without damaging healthy cells and tissues.  Young people like Angela will one day be at the forefront of research trying to solve many of the complex health problems facing large populations of citizens everywhere. I am excited as an individual that serious medical problem-solving is now transitioning to the next generation who possess innovative ideas and who have the perseverance to build a scientific consensus around the most effective ways to diagnose and treat serious diseases.

Complex medical problems like cancer deserve a bit more in-depth reporting.  Therefore I will present this particular blog in three sections: (1) a review of worldwide and national statistics on the prevalence of cancer, (2) describe Angela Zhang’s science project and concepts, and (3) describe a promising future where nanotechnology is concerned.

Section 1

Cancer Statistics from the World Health Organization

Q: Are the number of cancer cases increasing or decreasing in the world?

A: Cancer is a leading cause of death worldwide and the total number of cases globally is increasing.

The number of global cancer deaths is projected to increase 45% from 2007 to 2030 (from 7.9 million to 11.5 million deaths), influenced in part by an increasing and aging global population. The estimated rise takes into account expected slight declines in death rates for some cancers in high resource countries. New cases of cancer in the same period are estimated to jump from 11.3 million in 2007 to 15.5 million in 2030.

In most developed countries, cancer is the second largest cause of death after cardiovascular disease, and epidemiological evidence points to this trend emerging in the less developed world. This is particularly true in countries in “transition” or middle-income countries, such as in South America and Asia. Already more than half of all cancer cases occur in developing countries.

Lung cancer kills more people than any other cancer – a trend that is expected to continue until 2030, unless efforts for global tobacco control are greatly intensified. Some cancers are more common in developed countries: prostate, breast and colon. Liver, stomach and cervical cancer are more common in developing countries.

A number of common risk factors have been linked to the development of cancer: an unhealthy lifestyle (including tobacco and alcohol use, inadequate diet, physical inactivity), and exposure to occupational (e.g. asbestos) or environmental carcinogens, (e.g. indoor air pollution), radiation (e.g. ultraviolet and ionizing radiation), and some infections (such as hepatitis B or human papilloma virus infection).

Key risk factors for cancer that have been identified are:

  • tobacco use – responsible for 1.8 million cancer deaths per year (60% of these deaths occur in low- and middle-income countries);
  • being overweight, obese or physically inactive – together responsible for 274 000 cancer deaths per year;
  • harmful alcohol use – responsible for 351 000 cancer deaths per year;
  • sexually transmitted human papilloma virus (HPV) infection – responsible for 235 000 cancer deaths per year; and
  • occupational carcinogens – responsible for at least 152 000 cancer deaths per year.

Cancer prevention is an essential component of all cancer control plans because about 40% of all cancer deaths can be prevented.

CANCER STATISTICS IN THE UNITED STATES

The Centers for Disease Control and Prevention (CDC) provided the following statistics on cancer prevalence in the United States:

Cancer is the second leading cause of death in the United States, exceeded only by heart disease. In 2007, more than 562,000 people died of cancer, and more than 1.45 million people had a diagnosis of cancer, according to United States Cancer Statistics: 1999–2007 Cancer Incidence and Mortality Data.

The cost of cancer extends beyond the number of lives lost and new diagnoses each year. Cancer survivors, as well as their family members, friends, and caregivers, may face physical, emotional, social, and spiritual challenges as a result of their cancer diagnosis and treatment. The financial costs of cancer also are overwhelming. According to the National Institutes of Health, cancer cost the United States an estimated $263.8 billion in medical costs and lost productivity in 2010.

Racial and Ethnic Differences

Cancer can affect men and women of all ages, races, and ethnicities, but it does not affect all groups equally. For example, African Americans are more likely to die of cancer than people of any other race or ethnicity. In 2007, the age-adjusted death rate per 100,000 people for all types of cancer combined was 216 for African Americans, 177 for whites, 119 for American Indians/Alaska Natives, 117 for Hispanics, and 108 for Asians/Pacific Islanders.

Effective Cancer Prevention Measures

Opportunities exist to reduce cancer risk and prevent some cancers. Cancer risk can be reduced by avoiding tobacco, limiting alcohol use, limiting exposure to ultraviolet rays from the sun and tanning beds, eating a diet rich in fruits and vegetables, maintaining a healthy weight, being physically active, and seeking regular medical care.

Research shows that screening for cervical and colorectal cancer at recommended intervals can prevent these diseases by finding lesions that can be treated before they become cancerous. Screening also can help find cervical, colorectal, and breast cancers at an early, treatable stage. Vaccines also can reduce cancer risk.

The human papilloma virus (HPV) vaccine helps prevent some cervical, vaginal, and vulvar cancers. The hepatitis B vaccine can reduce liver cancer risk. Making cancer screening, information, and referral services available and accessible to all Americans can reduce cancer incidence and deaths.

Where You Live Matters

The following looks at Cancer Death Rates (2007) for each of the states. The death rates found in various states may simply reflect differences in the number of deaths by ethnicity reported earlier. However, explaining death rates in terms of ethnicity per se is a lot more complicated involving personal habits of diet and exercise, access to effective cancer treatment and health care, exposure to carcinogins, and differential genetic make-up, attitudes toward disease prevention, and tobacco use.

U.S.Cancer Death Rates,* 2007

127.9–170.7 171.1–180.7 181.0–191.9 193.3–213.7
Arizona Iowa Alaska Alabama
California Kansas Georgia Arkansas
Colorado Maryland Illinois Delaware
Connecticut Massachusetts Maine District of Columbia
Florida Montana Michigan Indiana
Hawaii Nebraska Missouri Kentucky
Idaho New Jersey Nevada Louisiana
Minnesota Oregon New Hampshire Mississippi
New Mexico Rhode Island North Carolina Ohio
New York South Dakota Pennsylvania Oklahoma
North Dakota Washington South Carolina Tennessee
Texas Wisconsin Vermont West Virginia
Utah Wyoming Virginia

* Rates are per 100,000 people and are age-adjusted to the 2000 U.S. standard population. Incidence rates are for about 99% of the U.S. population; death rates are for 100% of the U.S. population.

Source: United States Cancer Statistics: 1999–2007 Cancer Incidence and Mortality Data, available at http://www.cgc.gov/uscs.

Section 2

Angela’s Concept

Many times in the past I read of some promising new cure for cancer by the medical or scientific community.  When the public reads such articles relating to the “cause(s)” of cancer or some special “new technique” of treatment, there is always an emotional reaction and the hope that maybe this time a real cure for this devastating disease has at last been found. Too many times in the past the media would blow any new ideas on causation or treatment all out of proportion. Reality would soon take hold again, and in a heartbeat the public would once again get its hopes dashed.

So why am I so enthusiastic, and not just reserved, scientifically conservative, and cautiously optimistic this time? Everything in my gut tells me this time it may be for real. Am I’m only reacting to all this emotionally, or do you feel something important is occurring that warrants further consideration? Either way, please read on.

This is what Angela, doing a first class piece of research, came up with:

She basically created in the laboratory a nanoparticle that kills cancer. The nanoparticle is delivered to tumors via the drug salinomycin where it kills cancer cells and deposits gold and iron-oxide materials to help with MRI imaging.

The key word to remember is nanoparticle. Angela’s project was named, “Design of Image-guided, Photo-thermal Controlled Drug Releasing Multifunctional Nanosystem for the Treatment of Cancer Stem Cells.” It was apparently as complex, thorough, and revolutionary as it sounds.

Zhang’s achievement is impressive due to the level of understanding required to create such a nanoparticle in the first place and also because she is only 17 years old. She had spent over 1,000 hours since 2009 researching and developing the particle, and wants to go on to study chemical engineering, biomedical engineering, or physics. Her dream job is to be a research professor. Because cancer stem cells are so resistant to many forms of cancer treatment, Angela felt that this was an area worth focusing on. Her nanoparticle is award-winning due to the fact it has the potential to overcome cancer resistance while providing the ability for doctors to monitor the effects of the treatment using existing imaging techniques.

More specifically, Zhang developed a nanoparticle that can be delivered to the actual site of a tumor. Once there it kills the cancer stem cells. However, Zhang went further and included both gold and iron-oxide components, which allow for non-invasive imaging of the site through MRI and Photoacoustics. What makes this innovative approach so important is that normally cancer stem cells are very resistant to many forms of cancer treatment.

This can be a little difficult for non-scientists to understand, so I’ll do the best I can to explain her ideas and keep it simple. Angela’s basic idea was to mix cancer medicine in a polymer that would attach to nanoparticles. The nanoparticles in turn would then fasten themselves to cancer cells and show up on an MRI allowing doctors to know exactly where tumors are. An infrared light aimed at the tumors would then melt the polymer and release the medicine, killing the cancer cells while leaving healthy cells unharmed. When tested on mice the tumors almost completely disappeared. Although it will be years before scientists will be able to run tests on humans, the results do seem very promising.

 

I needed to understand some of the terminology myself particularly with reference to two important questions: What is a nanoparticle and what is a polymer?

What is a Nanoparticle?

A nanoparticle is an ultra fine unit with dimensions measured in nanometres (nm; billionths of a metre). Nanoparticles possess unique physical properties such as very large surface areas and can be classified as hard or soft. They exist naturally in the environment and are produced as a result of human activities. Owing to their submicroscopic size, they have unique material characteristics, and manufactured nanoparticles may find practical applications in a variety of areas, including medicine, engineering, catalysis, and environmental remediation. Examples of naturally occurring nanoparticles include terpenes released from trees and materials emitted in smoke from volcanic eruptions and fires. Quantum dots and nanoscale zero-valent iron are examples of manufactured nanoparticles.

What is a Polymer?

Polymers are made up of many molecules all strung together to form really long chains (and sometimes more complicated structures, too).

What makes polymers so interesting is that how they act depends on what kinds of molecules they’re made up of and how they’re put together. The properties of anything made out of polymers really reflect what’s going on at the ultra-tiny (molecular) level. So, things that are made of polymers look, feel, and act depending on how their atoms and molecules are connected. Some polymers are rubbery, like a bouncy ball, some are sticky and gooey, and some are hard and tough, like a skateboard.

Advances in polymer science have led to the development of several novel drug-delivery systems. A proper consideration of surface and bulk properties can aid in the designing of polymers for various drug-delivery applications. Biodegradable polymers find widespread use in drug delivery as they can be degraded to non-toxic monomers inside the body.

Novel supramolecular structures based on polyethylene oxide copolymers and dendrimers are being intensively researched for delivery of genes and macromolecules. Hydrogels that can respond to a variety of physical, chemical and biological stimuli hold enormous potential for design of closed-loop drug-delivery systems. Design and synthesis of novel combinations of polymers will expand the scope of new drug-delivery systems in the future.

Section 3

A Bright Future Ahead for Cancer Diagnosis and Treatment

The upshot of this Blog is to report that the future of cancer diagnosis and treatment looks very bright and promising. The thrust of this article is really about nanotechnology in medicine. The use of nanotechnology in medicine offers some exciting possibilities. Some techniques are only imagined, while others are at various stages of testing, or actually being used today.

Nanotechnology in medicine involves various applications of nanoparticles that are currently under development. Long term research involves the use of manufactured nano-robots. Their purpose is to make repairs at the cellular level (How exciting is that idea!).

// // Whatever you call it, the use of nanotechnology in the field of medicine could revolutionize the way we detect and treat damage to the human body and disease in the future, and many techniques only imagined a few years ago are making remarkable progress towards becoming realities.

Nanotechnology in Medicine Application: Drug Delivery

As I said earlier, one application of nanotechnology in medicine currently being developed involves employing nanoparticles to deliver drugs, but also heat, light or other substances to specific types of cells (such as cancer cells). Particles are engineered so that they are attracted to diseased cells which allow direct treatment of those cells. This technique reduces damage to healthy cells in the body and allows for earlier detection of disease.

// // Tests are in progress for targeted delivery of chemotherapy drugs and their final approval for their use with cancer patients is pending, as explained on CytImmune Science’s website. CytImmune has published the preliminary results of a Phase I Clinical Trial of their first targeted chemotherapy drug. For example, nanoparticles that deliver chemotherapy drugs directly to cancer.

Many researchers attach ethylene glycol molecules to nanoparticles that deliver therapeutic drugs to cancer tumors. The ethylene glycol molecules stop white blood cells from recognizing the nanoparticles as foreign materials, allowing them to circulate in the blood stream long enough to attach to cancer tumors. However, researchers at the University of California, San Diego believe that they can increase the time nanoparticles can circulate in the blood stream. They are coating nanoparticles containing therapeutic drugs with membranes from red blood cells and have shown that these nanoparticles will circulate in a mouse’s blood stream for almost two days, instead of the few hours observed for nanoparticles using ethylene glycol molecules.

Researchers are also continuing to look for more effective methods to target nanoparticles carrying therapeutic drugs directly to diseased cells. For example scientists are MIT have demonstrated increased levels of drug delivery to tumors by using two types of nanoparticles. The first type of nanoparticle locates the cancer tumor and the second type of nanoparticle (carrying the therapeutic drugs) homes in on a signal generated by the first type of nanoparticle (I thought this was brilliant).

If you hate getting shots, you’ll be glad to hear that oral administration for drugs that are currently delivered by injection may be possible in many cases. The drug is encapsulated in a nanoparticle which helps it pass through the stomach to deliver the drug into the bloodstream. There are efforts underway to develop oral administration of several different drugs using a variety of nanoparticles. A company which has progressed to the clinical testing stage with a drug for treating systemic fungal diseases is BioDelivery Sciences, which is using a nanoparticle called a cochleate.

Nanotechnology in Medicine Application: Therapy Techniques

What are some of the applications of nanotechnology related to therapy techniques? The following are some of the greatest scientific therapies currently being worked on:

  • Buckyballs that are used to trap free radicals generated during an allergic reaction and block the inflammation that results from an allergic reaction.
  • Nanoshells may be used to concentrate the heat from infrared light to destroy cancer cells with minimal damage to surrounding healthy cells. Nanospectra Biosciences has developed such a treatment using nanoshells illuminated by an infra laser that has been approved for a pilot trial with human patients.
  • Nanoparticles, when activated by x-rays, generate electrons that cause the destruction of cancer cells to which they have attached themselves. This is intended to be used in place of radiation therapy with much less damage to healthy tissue. Nanobiotix has released preclinical results for this technique.
  • Aluminosilicate nanoparticles can more quickly reduce bleeding in trauma patients by absorbing water, causing blood in a wound to clot quickly. Z-Medica is producing a medical gauze that uses aluminosilicate nanoparticles.
  • Nanofibers can stimulate the production of cartilage in damaged joints.
  • Nanoparticles may be used, when inhaled, to stimulate an immune response to fight respiratory viruses.

Nanotechnology in Medicine Application: Diagnostic and Imaging Techniques

Quantum Dots (qdots) may be used in the future for locating cancer tumors in patients and in the near term for performing diagnostic tests in samples. Invitrogen’s website provides information about qdots that are available for both uses, although at this time the use “in vivo” (in a living creature) is limited to experiments with lab animals. There can be a concern for toxicity based on the material quantum dots are made from. Because of this there is restriction involving the use of quantum dots in human patients. However, work is being done with quantum dots composed of silicon, which is believed to be less toxic than the cadmium contained in many quantum dots.

Iron oxide nanoparticles can also be used to improve MRI images of cancer tumors. The nanoparticle is coated with a peptide that binds to a cancer tumor, once the nanoparticles are attached to the tumor the magnetic property of the iron oxide enhances the images from the Magnetic Resonance Imagining scan.

Nanoparticles can attach to proteins or other molecules, allowing detection of disease indicators in a lab sample at a very early stage. There are several efforts to develop nanoparticle disease detection systems underway. One system being developed by Nanosphere, Inc. uses gold nanoparticles. Nanosphere has clinical study results with their Verigene system involving it’s ability to detect four different nucleic acids, while another system being developed by T2 Biosystems uses magnetic nanoparticles to identify specimens, including proteins, nucleic acids, and other materials.

Gold nanoparticles that have antibodies attached can provide quick diagnosis of the flu virus. When light is directed on a sample containing virus particles and the nanoparticles the amount of light reflected back increases because the nanoparticles cluster around virus particles, allowing a much faster test than those currently used.

Nanotechnology in Medicine Application: Anti-Microbial Techniques

One of the earliest nanomedicine applications was the use of nanocrystalline silver which is as an antimicrobial agent for the treatment of wounds, as discussed on the Nucryst Pharmaceutical website.

A nanoparticle cream has been shown to fight staph infections. The nanoparticles contain nitric oxide gas, which is known to kill bacteria. Studies on mice have shown that using the nanoparticle cream to release nitric oxide gas at the site of staph abscesses significantly reduced the infection.

Burn dressing that is coated with nanocapsules containing antibiotics. If an infection starts the harmful bacteria in the wound causes the nanocapsules to break open, releasing the antibotics. This allows much quicker treatment of an infection and reduces the number of times a dressing has to be changed.

A welcome idea in the early study stages is the elimination of bacterial infections in a patient within minutes, instead of delivering treatment with antibiotics over a period of weeks. You can read about design analysis for the antimicrobial nanorobot used in such treatments in the following article: Microbivors: Artificial Mechanical Phagocytes using Digest and Discharge Protocol.

Nanotechnology in Medicine Application: Cell Repair

Nanorobots could actually be programmed to repair specific diseased cells, functioning in a similar way to antibodies in our natural healing processes. Work is currently being done in a fantastic area of medicine. And that is the use of nanorobots in chromosome repair therapy.

Conclusions

These are exciting times to live in. Twenty years from now many of you reading this Blog may not be alive. But those of us who are older can take comfort in the knowledge that the health and well-being of our children and grandchildren does indeed look very promising. The scientific revolution rolls on, and society will certainly be a beneficiary from all of it.

 

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