Posts Tagged ‘prostate cancer’

Ultrasensitive Nanoparticle PSA Test Predicts If Prostate Cancer Will Return

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Posted 13 Jun 2010 — by James Street
Category Prostate Cancer

03 Jun 2010

Men who have just had their cancerous prostate gland removed have one pressing question for their doctors: Am I cured? But conventional tests haven’t been sensitive enough to provide a concrete answer. Current tests that measure the level of protein called PSA (prostate-specific antigen), which signals the presence of cancer, often detect no PSA, only to have cancer return in up to 40 percent of the cases.

New research from Northwestern University Feinberg School of Medicine and the University International Institute for Nanotechnology shows that an ultrasensitive PSA test using nanoparticle-based technology (VeriSens™ PSA, Nanosphere, Inc., research-use-only) may be able to definitively predict after surgery if the cancer is cured long term or if it will recur.

The new test, which is based upon assays invented at Northwestern in the laboratories of co-principal investigator Chad A. Mirkin, is 300 times more sensitive than currently available commercial tests and can detect a very low level of PSA that indicates the cancer has spread beyond the prostate. The test also may pick up cancer recurrence at a much earlier stage, when secondary treatment is most effective for a patient’s survival.

“This test may provide early and more accurate answers,” said co-principal investigator C. Shad Thaxton, M.D., an assistant professor of urology at Feinberg and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “It detects PSA at levels in the blood that cannot be detected by conventional tests. It may allow physicians to act at the earliest and most sensitive time, which we know will provide the patient with the best chance of long- term survival.”

This ability to quickly detect very low levels of PSA may enable doctors to diagnose men with prostate cancer recurrence years earlier than is currently possible. Prostate cancer is the second leading cause of cancer death for men in the United States.

Not only may the new test more accurately predict the course of the disease, it also gives an early indication of whether secondary treatments, such as radiation and hormone therapy, are working. If not, then doctors can quickly begin alternative treatment and refer patients to clinical trials.

The study results were presented June 2 at the American Urological Association 2010 Annual Meeting. These and the results of other Northwestern PSA studies were presented at the meeting by Lee Zhao, Dae Kim and Hannah Alphs, urology residents at Feinberg.

“These studies suggest that the nanotechnology PSA test might become the preferred postoperative PSA test for men who have been treated with radical prostatectomy,” said William Catalona, M.D., professor of urology at Feinberg, a physician at Northwestern Memorial Hospital and director of the clinical prostate cancer program at the Lurie Cancer Center. “It should be especially useful in the early identification of men who would benefit from adjuvant postoperative radiation therapy and those who need postoperative salvage radiation therapy for recurrence.” Catalona, a senior investigator on the study, was the first to demonstrate that the PSA test could be used as a screening test for prostate cancer.

The study confirms and builds on the previous findings of a 2009 pilot study Thaxton conducted with Mirkin, the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, and other colleagues.

PSA is a protein normally secreted out of the prostate cells into the semen in high concentrations. Usually, very little diffuses into the blood stream, and the normal PSA value for men without prostate disease is less than 2 nanograms per milliliter. When the prostate gland has a disease process, such as inflammation, benign enlargement or cancer, the barriers to PSA diffusion into the blood stream are breached, and PSA levels rise. In a man who has his cancerous prostate removed, there should be no PSA in the blood except for a minute amount produced by the periurethral glands. However, any PSA produced by cancer recurrence ends up in the blood stream and can be detected earlier with the more sensitive nanotechnology PSA assay.

For the new study, researchers obtained blood serum retrospectively from men whose PSA serum samples had been frozen after surgery and whose assays (blood analysis) showed an undetectable PSA level based on the conventional test. Northwestern researchers then tested those serum samples using the more sensitive nanotechnology-based test. They wanted to see if they could detect PSA at levels below the limit of the conventional test, and if those results could predict the cancer outcome for those patients, who were followed for up to 10 years.

Using the new test, Thaxton and colleagues found that the low and non-rising PSA levels (presumably produced by the normal periurethral glands) of patients meant that the prostate cancer was effectively cured and did not return over a period of at least 10 years. Scientists also found a PSA level higher than that expected from the periurethral glands based on the new test meant the patients would have their disease recur.

As result of the study, researchers were able to assign a PSA level number to a cure for the first time as well as a number that indicated the disease would recur and if it would recur aggressively. These newly identified levels were below what could have been detected with the conventional PSA test. The researchers were able to quantify PSA values at less than 0.1 nanograms per milliliter, the clinical limit of detection for commercial assays.

Thaxton said the next step for scientists is a prospective clinical trial to compare the nanoparticle-enhanced PSA assay to traditional PSA assays and determine if earlier detection and treatment can save lives.

Note:
Thaxton and Mirkin are shareholders in Nanosphere, Inc., the company that licensed the bio-barcode technology from Northwestern University.

Source:
Marla Paul
Northwestern University

Article URL: http://www.medicalnewstoday.com/articles/190754.php

Main News Category: Prostate / Prostate Cancer

Also Appears In:  Medical Devices / Diagnostics,

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Gamma-tocotrienol kills prostate tumour cells in animal model studies

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Posted 10 Apr 2010 — by James Street
Category Natural Therapies, Prostate Cancer

9. April 2010 09:45

Researchers from Davos Life Science in Singapore, in collaboration with scientists at the University of Hong Kong, have shown that gamma-tocotrienol, a member of the vitamin E family, is potent in killing prostate tumour cells in animal model studies. This research was reported this week in the latest edition of Pharmacology. These findings come soon after previously published research studies that demonstrated in-vitro evidence of gamma-tocotrienol’s cancer-killing capability for breast cancer and melanoma cells.

In this latest study, immuno-compromised mice with human-grafted prostate tumours were given two weeks’ dosing of gamma-tocotrienol. Researchers saw that gamma-tocotrienol was selectively deposited in solid tumours, and this led to over 50% tumour shrinkage. Linked to this tumour shrinkage ability, gamma-tocotrienol showed two effects associated with the killing of cancer cells. Firstly, there was a decrease in the expression of two cell proteins (PCNA and Ki67) associated with cell proliferation. Secondly, there was the activation of cellular processes called caspase cascades that are associated with programmed cell death. These inhibitive properties have been previously reported in studies investigating the effect of gamma-tocotrienol on breast cancer and melanoma. Together, these data suggest a common mechanism by which gamma-tocotrienol is able to reverse the growth of cancer cells.

This study also found that the anti-tumour effect of gamma-tocotrienol was mediated by the suppression of the NF-KB cell signaling pathway. NF-B is a protein that signals to the cell to produce chemicals that promote the body’s natural inflammation response and cell survival. Over activation of NF-B is associated with chronic inflammation. There is emerging evidence that chronic inflammation contributes to carcinogenesis and the development of malignancy in various organs, including the prostate, breast and skin.

“Previous studies have established natural tocotrienol as a promising opportunity for future R&D in cancer therapy and prevention,” said Dr. Daniel Yap, Deputy Head for Tocotrienol R&D, Davos Life Science Singapore, and one of the authors of the published paper. “This research contributes further evidence to this cause, showing that natural tocotrienol can potentially reduce the risks of diseases associated with chronic inflammation, including certain cancers.”

Combining gamma-tocotrienol with other chemotherapy treatments

The inhibition of tumour growth was achieved when used in a combination treatment of gamma-tocotrienol and Docetaxel (DTX). Currently, DTX is the first-line chemotherapy treatment in patients with prostate cancer that is resistant to hormone therapy. However, DTX can only extend the patient’s overall survival by an average of 2-3 months. As the gamma-tocotrienol’s anti-tumour effects were observed using physiologically-relevant doses that do not negatively affect animal health, this may provide a new treatment strategy that can improve the therapeutic efficacy of DTX against advanced stage prostate tumours, while reducing toxicity often seen in patients treated with DTX.

Gamma-tocotrienol is one of eight forms of vitamin E. It is found in low levels in food sources such as palm fruits, cereal grains and rice bran. The amount of gamma-tocotrienol found in palm oil is relatively higher than in other sources. In previous in-vitro studies, gamma-tocotrienol was shown to be able to kill prostate, melanoma, breast and pancreatic cancer cells.

Dr. Daniel Yap added, “In addition to this prostate cancer study, we are also advancing our Phase I clinical trial in the U.S. on pancreatic cancer. We expect to accelerate our tocotrienol research for the treatment and prevention of cancers. This latest study is yet another step forward in identifying potentially-effective naturally derived treatments that might have applications for cancer patients.”

SOURCE Davos Life Science

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