Targeted cancer therapy kills prostate tumor cells

A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds.

The results will be presented Saturday at The Endocrine Society’s 93rd Annual Meeting in Boston.

“This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer,” said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones.

This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

“These patients are left with very few treatment options and usually succumb quickly to the disease,” she said.

Ho’s team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer.

They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1.

They also gave G-1 to noncastrated, or “intact,” male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

“Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration,” Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitised prostate tumors to the cell growth-inhibiting effects of G-1.

“These results mean G-1 won’t work without androgen deprivation therapy,” she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy.

She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer.

“The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any estrogen related side effects.” she said.

Blood bubbles promise new treatments for brain disease

(Image: Eleanor Stride)

SCUBA divers are all too aware of the danger of bubbles of air forming in the blood.  

The bends can be lethal. But bubbles in the bloodstream are not always a bad thing. 

Much smaller bubbles can be used to deliver drugs, help prevent damage from stroke and even open up the blood-brain barrier, a discovery that could lead to new treatments for diseases of the brain.

A few decades ago, researchers discovered by chance that "microbubbles" of air in the blood made ultrasound images clearer and brighter. Now a group of researchers who call themselves "the bubble community" are finding new roles for these bubbles.

Ultrasound applied to microbubbles in the blood causes them to oscillate, which appears to boost the uptake of drugs and gene therapies into nearby cells, though how this works is unclear.

"The theory is that the bubbles are stimulating natural uptake mechanisms," says Eleanor Stride at University College London. "Exactly which mechanisms, we're not sure."

Stride's team has enhanced this effect by adding magnetic nanoparticles to the microbubbles. The group injected mice with a solution containing a gene for bioluminescence, and a suspension of bubbles, before magnetically dragging the bubbles to one lung and applying ultrasound there.

Three days later, the team found bioluminescence only in the target lung, confirming that the gene hadn't been expressed elsewhere. The findings were presented at the Institute of Electrical and Electronics Engineers Ultrasonics Conference in San Diego, California, last month.

Research finds surgery outperforms drug therapy in treatment of benign prostatic hyperplasia

Research finds surgery outperforms drug therapy in treatment of benign prostatic hyperplasia — Science Blog

A 17-year-long community study looking at symptoms of enlarged prostate in over 2,000 men age 40 to 79 years suggests that surgery for benign prostatic hyperplasia (BPH) offers more relief from incontinence and obstruction symptoms than treatment from drug-based therapy, according to a new study by researchers at Mayo Clinic. The researchers presented their results today at the annual meeting of the American Urological Association.

Overall, results show:

* Urinary incontinence was a common condition, coexisting with BPH/lower urinary tract symptoms.
* In the community setting, patients with the highest symptom scores were most likely to receive surgical intervention.
* Symptoms stabilised and did not get worse after treatment of all kinds.
* Patients who underwent transurethral resection of the prostate (TURP) had the greatest decrease in both symptoms and incontinence compared to other treatment groups. Pre-TURP the incontinence rate was 64.5 percent and post-TURP it was 41.9 percent.

Significance
The findings provide large-sample, long-term data comparing the effectiveness of medical versus surgical treatments in a large, general population, as compared to small, select clinical populations of men. “Our data fills a gap in the research record that can be used by physicians and patients to evaluate management options,” says Amy Krambeck, M.D., Mayo Clinic urologist and lead study investigator. “Because it’s a large community-based study of more than 2,100 men, it includes the entire broad range of male health. This suggests the results are stronger in terms of being generalised and applied to other men.”

Background
BPH and lower urinary tract symptoms, such as frequent urge to urinate or leakage, are common. By age 60, an estimated 50 percent of all men suffer from enlarged prostate symptoms; by age 90, about 80 percent do. Multiple treatments exist but data comparing drug therapy to surgery are lacking, making clinical decisions vulnerable to subjective factors.

About the Study
From 1990 through 2007, the study enrolled 2,184 healthy men, age 40-79, living in Olmsted County, Minn., All participants completed surveys every other year about their urinary symptoms and the treatments they received. From this information, the investigators examined urinary problems and incontinence before and after different types of treatment.

Results showed that of the 2,184 men:

* 1,574 (72%) received no treatment for BPH symptoms.
* 307 (14%) took alpha adrenergic receptor blockers (α-ARs).
* 195 (9%) took the medication 5-alpha-reductase inhibitors (ARIs).
* 23 (1%) received surgical laser vaporization.
* 85 (4%) received surgical transurethral resection of the prostate (TURP).

Comments Dr. Krambeck: “After intervention, the greatest improvement in symptom score was seen in the TURP group, followed by laser vaporisation, then the drugs, 5 alpha reductase inhibitors and alpha adrenergic receptor blockers.

Only the surgical TURP group reported a decrease in incontinence – pre-TURP the incontinence rate was 64.5 percent and post-TURP it was 41.9 percent.”

This reduction in incontinence rates is significant when compared to the increase in reported incontinence in the patients receiving both forms of medical therapy and no change in symptoms for patients receiving laser vaporization.