Ultrasound may help immune system detect cancer
High-intensity ultrasound beams aimed at tumours can cause them to 'leak', alerting the immune system to their presence, according to new research.
A study on mice, led by researchers at Duke University's Pratt School of Engineering, found that 'high-intensity focused' ultrasound (HIFU) can be used to physically shake tumour cells, causing the cell membranes to rupture and release their contents.
Once outside the cancer cell, the contents can be detected by the body's immune system, which can then produce anti-tumour white blood cells.
Although the technique has only been tested on mice so far, the researchers hope that it may provide a non-surgical treatment for humans that would induce the immune system to seek out and destroy cancer cells that have spread through the bloodstream into other parts of the body.
Pei Zhong, associate professor in the university's mechanical engineering and materials science department, commented: "In most cancers, what actually ends up killing the patient is the spread of the cancer from its original site to other parts of the body.
"If the patient has a tumour in the kidney or liver, several treatment options - including surgery, radiation or HIFU - can be used to get rid of the cancerous tissues. However, if the cancer cells spread to other vital organs such as the lung or brain, the outcomes are often much worse."
Dr Zhong revealed that HIFU is currently being tested in China, Europe and the US, where it is being used to kill tumours by heating them.
He explained that this method currently only enables doctors to treat the primary tumour, but said that using mechanical vibration to shake and break apart tumour cells "may have an even more significant impact in suppressing cancer metastasis by waking up the immune system".
"Our results show that while mechanical HIFU is not as effective as thermal HIFU in killing tumour cells directly, it has the potential to induce a stronger anti-tumour immune response," Dr Zhong said.
"These preliminary findings open up the possibility that we could use heat from HIFU to treat the primary tumour and HIFU-boosted immunotherapy for combating any residual and metastatic tumour cells."
The study is published in the Journal of Translational Medicine.
Research into the causes, prevention, and treatment of prostate is under way in many medical centers throughout the world.
Genetics
New research on genes linked to prostate cancer is helping scientists better understand how prostate cancer develops. These studies are expected to provide answers about the genetic changes that lead to prostate cancer. This could make it possible to design medicines to reverse those changes. Tests to find abnormal prostate cancer genes could also help identify men at high risk who would benefit from more intensive screening or from chemoprevention trials, which use drugs to try to keep them from getting cancer.
Most of the genes that have been studied so far are from chromosomes that are inherited from both parents. One recent study found that a certain variant of mitochondrial DNA, which is inherited only from a person's mother, might double or even triple a man's risk of developing prostate cancer.
An exciting new development in genetics research is the use of DNA microarray technology which allows scientists to study thousands of genes at the same time. Using this method, researchers have identified several genes now thought to play a role in prostate cancer. This may eventually provide more sensitive screening tests for prostate cancer than the PSA blood test currently in use.
One of the biggest problems now facing men with prostate cancer and their doctors is figuring out which cancers are likely to stay within the gland and which are more likely to grow and spread (and definitely need treatment). New discoveries may help with this some time in the near future. For example, the product of one gene identified by DNA microarray, known as EZH2, seems to appear more often in advanced prostate cancers than in those at an early stage. Researchers are now trying to decide whether the presence of this gene product, or others, indicates that a cancer is more aggressive. This could eventually help tell which men need treatment and which might be better served by watchful waiting.
Prevention
Researchers continue to look for foods that increase or decrease prostate cancer risk. Scientists have found some substances in tomatoes (lycopenes) and soybeans (isoflavones) that may help prevent prostate cancer. Studies are now looking at the possible effects of these compounds more closely. Scientists are also trying to develop related compounds that are even more potent and might be used as dietary supplements. So far, most research suggests that a balanced diet including these foods as well as other fruits and vegetables is of greater benefit than taking these substances as dietary supplements.
Some studies suggest that certain vitamin and mineral supplements (such as vitamin E and selenium) may lower prostate cancer risk. A large study of this issue, called the Selenium and Vitamin E Cancer Prevention Trial (SELECT), is still in progress. Another vitamin that may be important is vitamin D. Recent studies have found that men with high levels of vitamin D seem to have a lower risk of developing the more lethal forms of prostate cancer.
Although many people assume that vitamins are natural substances that cause no harm, recent research has shown that high doses may be harmful. One study found that men who take more than 7 multivitamin tablets per week may have an increased risk of developing advanced prostate cancer.
Scientists are also testing certain hormonal medicines as a way of reducing prostate cancer risk. Finasteride (Proscar) and dutasteride (Avodart) are drugs that lower the body's levels of a potent androgen called DHT. Both drugs are already used to treat benign prostatic hyperplasia (BPH). The results of one such study, the Prostate Cancer Prevention Trial are discussed above in the section, "Can Prostate Cancer Be Prevented?" This study looked at the possible benefits of finasteride, although the results were not clear-cut. Another study is looking at whether dutasteride might be helpful in reducing the risk of getting prostate cancer.
Early Detection
Doctors agree that the PSA blood test is not a perfect test for finding prostate cancer early. It misses some cancers, and in other cases it is elevated when cancer isn't present. Researchers are working on two strategies to address this problem.
One approach is to try to improve on the test that measures the total PSA level, as described in the section, "Can Prostate Cancer Be Found Early?" The percent-free PSA is one way to do this, although it requires two separate tests. Another option might be to measure only the "complexed" PSA (the portion of PSA that is not "free") to begin with, instead of the total and free PSA. This one test could give the same amount of information as the other two done separately. Studies are now under way to see if this test provides the same level of accuracy.
The other approach is to develop new tests based on other tumor markers. Several newer blood tests seem to be more accurate than the PSA test, based on early studies. One example is a blood test for a marker called EPCA-2. Another approach is to look for signs of the body's own immune reaction to substances made by prostate cancer cells. While early results have been promising, these and other new tests are not yet available outside of research labs and will require more study before they are widely used to test for prostate cancer.
Diagnosis
Doctors performing prostate biopsies often rely on transrectal ultrasound (TRUS), which creates black and white images of the prostate using sound waves, to know where to take samples from. But standard ultrasound may not detect some areas containing cancer. A fairly new technique, known as color Doppler ultrasound, measures blood flow within the gland. (Tumors often have more blood vessels around them than normal tissue.) It may make prostate biopsies more accurate by helping to ensure the right part of the gland is sampled. An even newer technique may enhance color Doppler further. It involves first injecting the patient with a contrast agent containing microbubbles. Promising results have been reported, but more studies will be needed before its use becomes common.
Staging
Staging plays a key role in deciding which treatment options a man may be eligible for. But imaging tests for prostate cancer such as CT and MRI scans can't detect all cancers, especially small areas of cancer in lymph nodes. A newer method, called enhanced MRI, may help find lymph nodes that contain cancer. Patients first have a standard MRI. They are then injected with tiny magnetic particles and have another scan done the next day. Differences between the 2 scans point to possible cancer cells in the lymph nodes. Early results of this technique are promising, but it needs more research before it becomes widely used.
Treatment
This is a very active area of research. Newer treatments are being developed, and improvements are being made among many standard prostate cancer treatment methods.
Surgery
If the nerves that control erections (which run along either side of the prostate) must be removed during the operation, a man will become impotent. Some doctors are now exploring the use of sural nerve grafts to try to restore potency if the original nerves must be removed. This approach, done at the same time as the radical prostatectomy, involves replacing the original nerves with small nerves taken from the side of the foot. This is still considered an experimental technique, and not all doctors agree as to its usefulness. Further study is under way.
Radiation Therapy
As described in the section, "How Is Prostate Cancer Treated?" advances in technology are making it possible to aim radiation more precisely than in the past. Currently used methods such as conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) allow doctors to treat only the prostate gland and avoid radiation to normal tissues as much as possible. This is expected to increase the effectiveness and reduce the side effects of radiation therapy. Studies are being done to find out which radiation techniques are best suited for specific groups of patients with prostate cancer.
Newer forms of radiation therapy that deliver radiation from several angles, such as the CyberKnife and helical tomotherapy, may provide even more precise delivery of radiation to the prostate while sparing normal tissues. These newer approaches have only been available for a short time, so there is limited data on them.
Technology is making other forms of radiation therapy more effective as well. New computer programs allow doctors to better plan the radiation doses and approaches for both external radiation therapy and brachytherapy. Planning for brachytherapy can now even be done during the procedure (intraoperatively).
Newer Treatments for Localized Disease
Researchers are looking at newer forms of treatment for early stage prostate cancer. These new treatments could be used either as the first type of treatment or be used after radiation therapy in cases where it was not successful.
One promising treatment, known as high-intensity focused ultrasound (HIFU), destroys cancer cells by heating them with highly focused ultrasonic beams. While it has been used more in Europe, it is not commonly employed in the United States at this time. Studies are now under way to determine its safety and effectiveness.
Nutrition and Lifestyle Changes
A recent study found that in men with a rising PSA after surgery or radiation therapy, drinking pomegranate juice seemed to slow the time it took the PSA level to double. Larger studies are now under way to try to confirm these results.
Some encouraging early results have also been reported with flaxseed supplements. One small study in men with early prostate cancer found that daily flaxseed seemed to slow the rate at which prostate cancer cells multiplied. More research is needed to confirm this finding.
A recent report found that men who chose not to have treatment for their localized prostate cancer may be able to slow its growth with intensive lifestyle changes. The men ate a vegan (no meat, fish, eggs, or dairy products) diet and exercised frequently. They also took part in support groups and yoga. After one year the men saw, on average, a slight drop in their PSA level. It isn't known whether this effect will last since the report only followed the men for 1 year. The regimen may also be hard to follow for some men.
Chemotherapy
Studies in recent years have shown that many chemotherapy drugs can affect prostate cancer. At least one drug (docetaxel) has been shown to help men live longer. Several new chemotherapy drugs and combinations of drugs are now being studied.
One newer drug is satraplatin, which is in late-stage clinical trials as a second-line chemotherapy option for men with advanced, hormone-refractory prostate cancer. Satraplatin is taken as a pill. It is now being looked at by the FDA for possible approval.
Calcitriol, a form of vitamin D, has recently shown promising results when combined with docetaxel (Taxotere). Men who received the combination seemed to do better than men in other studies who received only docetaxel. A large clinical trial is now comparing a high-dose form of calcitriol (DN-101) and docetaxel to docetaxel alone.
Prostate Cancer Vaccines
Several types of vaccines for boosting the body's immune response to prostate cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, prostate cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects. At this time, vaccines are only available in clinical trials.
The furthest along in terms of development is sipuleucel-T (Provenge). For this vaccine, dendritic cells (cells of the immune system) are removed from the patient's blood and exposed to a part of prostate cancer cells called prostatic acid phosphatase (PAP). These cells are then put back into the body where they induce other immune system cells to attack the patient's prostate cancer. A small study found that the vaccine seemed to increase survival in men with advanced, hormone-refractory prostate cancer, and further studies are under way. Provenge is now being looked at by the FDA for possible approval.
A vaccine known as GVAX has also shown promise against advanced, hormone-refractory prostate cancer in early studies. This vaccine is made up of prostate cancer cells that have been genetically modified to make GM-CSF, a substance that boosts the immune response against them. GVAX is now in late-stage clinical trials.
Another prostate cancer vaccine (PROSTVAC-VF) uses a virus that has been genetically modified to contain prostate-specific antigen (PSA). The patient's immune system should respond to the virus and begin to recognize and destroy cancer cells containing PSA. This vaccine is still in early-stage clinical trials.
Several other prostate cancer vaccines are also in development.
Monoclonal Antibodies
Monoclonal antibodies are manmade versions of immune system proteins designed to target specific molecules in prostate cancer cells. Several different ones are being developed and tested.
For example, pertuzumab is a monoclonal antibody directed against the HER2 protein, which is sometimes found in excess amounts on the surface of cancer cells. Studies of men with advanced, hormone-refractory prostate cancer have not found that pertuzumab shrinks tumors or lowers PSA levels, although one study found it may have helped men live longer than would be expected.
Angiogenesis Inhibitors
Growth of prostate cancer tumors depends on growth of blood vessels (angiogenesis) to nourish the cancer cells. Looking at angiogenesis in prostate cancer specimens may help predict treatment outcomes. Cancers that stimulate many new vessels to grow are harder to treat and have a poorer outlook.
New drugs are being studied that may be useful in stopping prostate cancer growth by keeping new blood vessels from forming. Several anti-angiogenic drugs are already being tested in clinical trials. One of these is thalidomide, which has been approved by the FDA to treat patients with multiple myeloma. It is being combined with chemotherapy in clinical trials to treat men with advanced prostate cancer. While promising, this drug can cause major side effects, including constipation, drowsiness, and nerve damage.
Another drug, bevacizumab (Avastin), is FDA-approved to treat patients with other cancers. It is now being tested in combination with hormone therapy and chemotherapy in men with advanced prostate cancer.
Treatment of Bone Pain
Doctors are now studying the use of radiofrequency ablation (RFA) to help control pain in men whose prostate cancer has spread to one or more areas in the bones. During RFA, the doctor uses computed tomography (CT) or ultrasound to guide a small metal probe into the area of the tumor. A high frequency current passed through the probe heats and destroys the tumor. While RFA has been used for many years to treat tumors in other organs such as the liver, its use in treating bone pain is still fairly new.
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