Silver and Gold ‘nanocages’ might buy early detection

By Sara Braniecki

Researchers from Washington University and Purdue University collaborated to experiment with a new medical imaging technique that they hope will lead to early detection and treatment for cancer patients.  The procedure uses a pulsed laser and tiny metallic “nanocages, as the researchers call them, to create images much clearer than those created using previous techniques.

This composite image shows luminous nanocages, which appear like stars against a black background, and a living cell, at upper left. The gold-silver nanocages exhibit a bright "three-photon luminescence" when excited by the ultrafast pulsed laser, with 10-times greater intensity than pure gold or silver nanoparticles. The signal allows live cell imaging with negligible damage from heating.

The nanocages are injected into the bloodstream, and then laser pulses are shone through the patient’s skin to detect them. The nanocages are small, hollow spheres made of a combination of gold and silver. Both the nanocages are only 40 nanometers wide.  To put that into perspective, this is 100 times smaller than a red blood cell.  The laser shines light that is almost infrared and pulses 80 million times per second.

The procedure illuminates tissues and organs, allowing live cell imaging.  The precision of these images is important for accurate detection and thorough treatment of cancer.

The images produced using this technique provide a much better image than older techniques that used nanospheres made solely of gold.  The new images have greater contrast since there is less background glow of surrounding tissues.  One of the researchers from Purdue University, Ji-Xen Cheng, explains, “This lack of background fluorescence makes the images much more clear and is very important for disease detection.  It allows us to clearly identify the nanocages and the tissues.”

Another advantage of using the nanocages made of both silver and gold is that there is no resulting heat damage in the tissue.  Previously, the image needed to be enhanced to get a clear enough image that was usable.  To enhance the image, clouds of electrons moving in unison had to be induced in the tissue- this resulted in the heat damage.  Since this enhancement is no longer vital, the heat damage does not occur.

The researchers hope that the creation of the nanocages will lead to better detection and treatment.  Washington University researcher Younan Xia, whose team engineered the nanocages, explains that the productions of the nanocages will likely allow researchers “to combine imaging and therapy for better diagnosis and monitoring.”  He also foresees that the nanocages might be used to deliver time-released anticancer drugs to diseased tissue.

Further information.

Wait for Prostate Treatment May Be Over

April 18, 2010

By: Shelly Hwang

Prostate cancer is the second-leading cause of cancer death in men, with men having a one in six chance that they will get prostate cancer in their lifetime. While prostate cancer can be treated with surgery, a new treatment similar to radiation is being tested that may be able to more effectively target proteins on the surface of prostate tumors, providing hope even for patients with advanced prostate cancer.

Human prostate cancer cells can be recognized by overexpression of some proteins on their surface. The abundance of certain proteins provides a way to target these cancer cells by using antibodies. The antibodies will be binded to the isotope 212-lead, which is an altered form of the common element lead. When this antibody is injected into a patient’s veins, it will bind to a tumor’s surface and release particles and radiation that will destroy only the tumor cells.

Researchers in Zhongyun Dong’s laboratory at the University of Cincinnati are getting ready to test this new agent over the course of this year. They will measure how toxic and effective the treatment is in slowing down or blocking cancer cell growth. Then, the treatment will be used in clinical trials with patients with advanced prostate cancer.

Original Press Release

UC Academic Health Center

Melanoma, Soon to be “Mela-no-more”?

By Nick Gubitosi

Just last week (April 6, 2010), scientists at the Rush University Medical Center in Chicago completed the second phase of trials for a very promising melanoma vaccine.  The trial, which had stunning results, was conducted on 50 patients with metastatic melanoma, which is melanoma that had spread to multiple parts of the body.  Currently treatments for advanced melanoma include chemotherapy and immunological drugs which are only effective 15 % of the time.  This new vaccine is not only easy to administer, but it also appears to have a much higher response rate in patients, potentially making it the best treatment option for anyone with advanced melanoma.

Melanoma is a rare but deadly cancer that typically begins in a mole or other pigmented tissue and can easily be removed if caught early.  If it advances it is much harder to treat and without treatment the patient usually has only a few years to live.

The vaccine being tested in this study is known as OncoVEX.  OncoVEX is effective because it is composed of an oncolytic virus, or a reprogrammed virus that is made to attack cancerous cells while leaving healthy cells undamaged.  The vaccine is injected directly into lesions that can be felt or seen, and its ease of administration allows it to be given right in a physician’s office.

According to Dr. Howard Kaufman, the director of the Rush Cancer Program, “The vaccine worked not just on the cells we injected, but on lesions in other parts of the body that we couldn’t reach.”  He explains how these injections prompt an immune response that circulates through the bloodstream to other affected parts of the body.

In the second phase of trials for OncoVEX, 50 patients were given up to 24 injections of the vaccine over the course of several months, leading to 4 partial and 8 full recoveries.  The scientists found these results very promising and Kaufman stated that, “These are the best results to date for any vaccine developed for melanoma, but they need to be confirmed in a larger population.”

To confirm these results, Kaufman is set to lead a third phase of trials which will enroll approximately 430 patients from cancer centers across the U.S.  These patients will be tracked for two years after their first dose and if the results are anything like the previous trial, this vaccine could turn an advanced melanoma diagnosis from a death notice into a treatable disease.

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Tricky tumors grow and spread

The tumor has transformed its outer layer to mimic lymph node tissue to avoid detection by the immune system.

By Sara Braniecki

Researchers from Switzerland’s Ecole Polytechnique Fédérale de Lausanne (EPFL) published a study in the March 2010 issue of Science explaining how tumor cells avoid being destroyed by the immune system.  The researchers believe that knowing how cancerous cells avoid the body’s immune system could lead to a future understanding of how to use the body’s natural defense mechanism to destroy cancerous cells.

Tumors make themselves and the surrounding area seem perfectly normal by disguising themselves as lymph nodes, which are a key part of the immune system that filters the blood and traps foreign particles.  Due to the disguise, the immune system is not phased and has no reason to take any destructive action on the cancer cells.

The researchers focused on a protein in genuine lymph nodes that attracts cells and instructs them to carry out defensive functions for the body.  Some tumors make their outer layer, with which the immune system would come into contact, appear as lymph node tissue by secreting this protein that the researchers were studying.  Since the tumors secrete the protein, they attract immune cells.   The immune cells are tricked into thinking the tumor is healthy rather than foreign.  Thus the tumor is not destroyed by the immune system, allowing it to grow and spread.

According to one of the researchers, Jacqui Shields, the concept that tumors mimic lymphoid tissue to alter the host’s immune response represents a new understanding of tumors’ interactions with the lymphatic system.  This will possibly open up a new area of study, and hopefully open up new understanding for cancer therapy.

Further information.

The key to locking up cancer

Sara Braniecki

Structure of TGF-B

In the current issue of Nature Cell Biology, a team of researchers led by Philip Howe from the Department of Cancer Biology at the Lerner Research Institute explain how they worked backwards to discover the protein that triggers cancer cells to be released from the original tumor, thus giving rise to new tumors.  Knowing this can lead to the development of drugs that contain cancer to one location, making it more efficiently treatable.

The researchers already knew that a process called epithelial-mesenchymal transdifferentiation (EMT) was important for cells on the surface of a tumor to transform into cells that are able to grow a new tumor elsewhere in the body.  The researchers worked backwards through the EMT process to find out what initiates it.  The researchers discovered that a protein called disabled-2 (Dab2) activated the EMT process and Dab2’s formation was triggered by transforming growth factor-b (TGF-b).

The EMT process is often what leads to death in patients with breast, ovarian, pancreatic, and colon-rectal cancers.  With the information these researchers have discovered about cancer cells, researchers can now begin to create drugs to stop EMT and stop cancer from spreadings.  This information could also lead to understanding how other diseases progress and can be contained.

Further Information.

Bullet shaped virus may be the future of new cancer and HIV treatments

By Liz Humes

An obscure virus that does not harm human cells has been generating a wave of excitement in the scientific community.  So what is the big deal?  A team of researchers from UCLA has reported the 3D structure of the vesicular stomatitis virus (VSV) in a break-through study published in the February 5th edition of Science (full article).  Their findings may shed light on how VSV can be manipulated and used in the treatment of cancer and in the development of vaccines for HIV and other harmful viruses.

The researchers used advanced, cutting-edge imaging techniques to visualize the 3D structure of VSV, which appears to have a bullet shaped head and cylindrical trunk.  They also characterized how the virus comes to form this bullet shape.  With this additional level of understanding of the physical structure of the virus, scientists believe that they can find ways to modify the structure of the virus and use it to treat and prevent illnesses such as cancer and AIDS.

As author Z. Hong Zhou remarked, “This work moves our understanding of the biology of this large and medically important class of viruses ahead in a dramatic way.”

VSV is a model virus that scientists use in the laboratory to study dangerous viruses that cause illnesses such as the flu, measles, and rabies.  Previous studies have shown that VSV can detect and kill human cancer cells.  Other studies have addressed the question of how to manipulate the virus to deliver a vaccine against HIV to the human body.

3D animation of VSV trunk

(Video is a 3D animation of the lower trunk structure of VSV-source)

A closer look at vaccine technology

A current trend in vaccine development is to use harmless viruses as “vectors” that can carry a specific vaccine to human cells.  These viruses have been engineered in the laboratory to carry pieces of genetic material from other pathogens and when they attach to human cells, they inject this genetic material into the cells.  These actions mirror an infection by the pathogen itself, although the virus vector does not actually cause an infection, and stimulates an immune response.  The human body then remembers how to respond to this pathogen the next time it encounters the pathogen and the body is protected from infection.

Modified versions of the viruses that cause the common cold and small pox are being studied in addition to VSV for use as vaccine vectors.  Given the potential that this type of vaccination has to prevent deadly infections from viruses and bacteria, this is an area of research one should surely keep an eye on.

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Press release

Vaccination information

HIV vaccination development

Old Chinese Medicine, New Cancer Treatment

Sara Braniecki

    Dr. Ahmed Chadli and fellow researchers at the Medical College of Georgia believe that they are on the right track to finding a new cancer treatment using celastrol, a plant derivative derived from trees and shrubs called celastracaea that the Chinese have used to treat symptoms such as fever, chills, and inflammation for centuries.

    Dr. Chadli and his colleagues think that they can devise a way for celastrol to be used for cancer treatment by using it to inactivate P23, a protein required for cancer growth.  Normally, P23 is a chaperone protein aiding the heat shock protein 90 (Hsp90).  Hsp90 has many chaperone proteins for its many different functions, and it is challenging for researchers to find a chaperone protein that will selectively target the Hsp90 implicated in a specific tumor.  The MCG researchers believe that celastrol has the specificity to control cancer cell growth by forcing the Hsp90 to cluster together, inactivating it.

    “Cancer cells need Hsp90 more than normal cells because cancer cells have thousands of mutations.  They need chaperones all the time to keep their mutated proteins active.  By taking heat shock proteins away from cells, the stabilization occurs and cell death occurs,” explains Dr. Chadli.

Dr. Chadli in the laboratory
Dr. Chadli researching in the laboratory.

 

Dr. Chadli is a researcher and professor at the Medical College of Georgia and an alumnus of the Mayo Clinic.  He has been researching Hsp90 for over 10 years and has several works published in The Journal of Biological Chemistry and other journals.  He conducts thorough research to understand the intricacies of all the molecules and pathways associated with Hsp90.  Cancer therapy can be greatly refined with ambitious research like his.  Dr. Chadli looks forward to future studies on cancer patients with greater dosage of celastrol, hopefully leading to greater results in the therapy.

Further information.