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Lethal 'Lint Brush' Captures and Kill Cancer Cells E-mail
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In a new tactic in the fight against cancer, Cornell University researcher Michael King has developed what he calls a lethal "lint brush" for the blood -- a tiny, implantable device that captures and kills cancer cells in the bloodstream before they spread through the body.

The strategy, which takes advantage of the body's natural mechanism for fighting infection, could lead to new treatments for a variety of cancers, said King, who is an associate professor of biomedical engineering.

In research conducted at the University of Rochester and to be published in an upcoming issue of the journal Biotechnology and Bioengineering, King showed that two naturally occurring proteins can work together to attract and kill as many as 30 percent of tumor cells in the bloodstream -- without harming healthy cells.

King's approach uses a tiny tubelike device coated with the proteins that could hypothetically be implanted in a peripheral blood vessel to filter out and destroy free-flowing cancer cells in the bloodstream.

To capture the tumor cells in the blood, King used selectin molecules --proteins that move to the surface of blood vessels in response to infection or injury.
Selectin molecules normally recruit white blood cells (leukocytes), which "roll" along their surfaces and create an inflammatory response -- but they also attract cancer cells, which can mimic the adhesion and rolling process.

Once the cancer cells adhered to the selectin on the microtube's surface, King exposed them to a protein called TRAIL (for Tumor Necrosis Factor Related Apoptosis-Inducing Ligand), which binds to two so-called "death receptors" on the cancer cells' surface, setting in motion a process that causes the cell to self-destruct.

The TRAIL then releases the cells back into the bloodstream to die; and the device is left free to work on new cells.

"It's a little more sophisticated than just filtering the blood, because we're not just accumulating cancer cells on the surface," King said.

King's research showed that the device can capture and kill about 30 percent of cancer cells flowing past it a single time, with the potential to kill more in the closed-loop system of the body. Used in combination with traditional cancer therapies, King said, the device could remove a significant proportion of metastatic cells, "and give the body a fighting chance to remove the rest of them."

The team also showed that a system in which the cancer cells "roll" over the target molecules - presenting their entire surface to the molecules - is four times more effective than a static setup in which the cells and proteins make contact at a single point.

King's group tested the device on prostate and colon cancer cells, but noted that it could also be customized with additional peptides or other proteins to target other types of cancer cells. "And if you could reduce or prevent metastasis, pretty much any cancer would be treatable," he said.

But translating the research into a clinical application will take time, he added, and is still likely years away.

"The actual physical device, when it gets eventually tested in humans, will probably look a lot like an arteriovenous shunt [a small tube, or shunt, that diverts blood flow] with our protein coating," he said.

"This has never been tried before. It's a whole new way of approaching cancer treatment," he added. "There's a lot of work yet to be done, of course, before this actually helps people -- but this is how it starts."

Other authors on the paper include Kuldeep Rana, a Cornell Ph.D. student, and Jane Liesveld, M.D., a clinician at the University of Rochester. The research was funded by New York state and the National Cancer Institute.

About Cancer

Cancer (medical term: malignant neoplasm) is the general name for a group of more than 100 diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer cells can spread to other parts of the body through the blood and lymph systems. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer that begins in basal cells of the skin is called basal cell carcinoma.

Cancer types can be grouped into broader categories. The main categories of cancer include:
  • Carcinoma - a cancer which is derived from the lining cells, or epithelium, of an organ. There are 4 major types of epithelium in the body (Glandular, squamous, transitional, and pseudostratified). Some types are only found in a few select organs such as the lung (pseudostratified) or urinary bladder (transitional).  Carcinomas can arise from any of these epithelial types. For example, breast carcinoma is most commonly derived from the lining cells of the milk producing glands. A carcinoma with a glandular growth pattern is an adenocarcinoma.  Common adenocarcinomas include prostate, colon, and breast.  A carcinoma with a growth pattern resembling the squamous lining cells is termed a squamous cell carcinoma.  Common squamous cell carcinomas are found in the esophagus and skin.  However, any of these organs may have either type of carcinoma arising from it, although these latter diagnoses are exceedingly rare.
  • Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
  • Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
  • Lymphoma - a cancer derived from the white blood cells that are present in the lymphoid tissues of the body.  These sites most commonly include the lymph nodes and spleen. However, lymphomas may arise from any organ and body site.
  • Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking, limiting time in the sun, being physically active, and eating a better diet. Half of all men and one-third of all women in the US will develop cancer during their lifetimes.

Although doctors often cannot explain why one person develops cancer and another does not, research shows that certain risk factors increase the chance that a person will develop cancer. Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or viruses, bacteria, and certain hormones. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth.  Other common risk factors for cancer include:
  • Growing Older
  • Family history of cancer
  • Poor diet, lack of physical activity, or being overweight
  • Alcohol

About The Bioengineering and Biotechnology Journal

The journal Bioengineering and Biotechnology is available at http://www3.interscience.wiley.com/journal/117901490/issue. The article is titled "Delivery of apoptotic signal to rolling cancer cells: a novel biomimetic technique using immobilized TRAIL and E-selectin" DOI: 10.1002/bit.22204.

Chronicle story link: http://www.news.cornell.edu/stories/Dec08/king.cancer.html
 
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