The Cancer Institute of new Jersey Explores Blocking Mechanism for Cancer Cell Survival

Newswise — Building upon recent laboratory discoveries on resistance by cancer cells to therapies that attempt to starve cancer, scientists at the Cancer Institute of new Jersey (CINJ) are conducting a clinical trial that further explores how to prevent that action. the goal is to discover if an anti-malaria drug approved by the Food and Drug Administration is able to block a cellular process that acts as a survival method for malignant cells in human melanoma, the most life threatening form of skin cancer. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School and new Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center — one of only 40 in the country.

Hydroxychloroquine, which is commonly used to treat malaria and certain types of arthritis, has been shown to block autophagy, the process by which cells eat themselves in order to survive through times of stress. this process allows cells to become resistant to cancer therapies. Research by CINJ Associate Director for Basic Science, Eileen White, PhD, adjunct professor of surgery at UMDNJ-Robert Wood Johnson Medical School and professor of molecular biology and biochemistry at Rutgers, the State University of new Jersey, and other laboratories at CINJ indicates that drugs such as hydroxychloroquine may help cancer treatments work more effectively by providing an easier path for the cancer drugs to enter the cell.

In this trial, investigators want to learn how to detect the process of autophagy in humans with melanoma, a goal lead researcher Janice Mehnert, MD, medical oncologist at CINJ and assistant professor of medicine at UMDNJ-Robert Wood Johnson Medical School, says is key. “By further examining the process of autophagy and learning if hydroxychloroquine is able to interrupt this process in human blood and tumor samples, we may be able to find a way to maximize the benefit of hydroxychloroquine in order to improve clinical outcomes,” she said.

Adults with stage III or stage IV melanoma tumor or tumors (cancer that has spread beyond where it first occurred) who can be scheduled for surgery to either cure the cancer or lessen the symptoms of cancer are eligible to take part in the trial, although other criteria must be met. Patients with newly diagnosed melanoma tumors or who have disease that has returned also are eligible to participate. Prior to being accepted into the study, participants would undergo a number of tests including blood work and a physical.

If accepted for participation in the trial, individuals will take a hydroxychloroquine pill each day for two weeks leading up to surgery. Participants will keep a pill diary and undergo periodic blood work during this time.

For more information on how to take part, individuals should call CINJ’s Office of Human Research Services at 732-235-8675 or e-mail cinjclinicaltrials@umdnj.edu.

The trial is supported by grants from the National Cancer Institute and the Harry Lloyd Foundation.

Clinical trials, often called cancer research studies, test new treatments and new ways of using existing treatments for cancer. at CINJ, researchers use these studies to answer questions about how a treatment affects the human body and to make sure it is safe and effective. there are several types of clinical trials that are currently underway at CINJ, including those that diagnose, treat, prevent, and manage symptoms of cancer. Many treatments used today, whether it is drugs or vaccines; ways to do surgery or give radiation therapy; or combinations of treatments, are the results of past clinical trials.

As new Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, CINJ offers patients access to treatment options not available at other institutions within the state. CINJ currently has more than 1,000 patients enrolled in clinical trials, including approximately 15 percent of all new adult cancer patients and approximately 70 percent of all pediatric cancer patients. Enrollment in these studies nationwide is fewer than five percent of all adult cancer patients.

About the Cancer Institute of new JerseyThe Cancer Institute of new Jersey (cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center dedicated to improving the detection, treatment and care of patients with cancer, and serving as an education resource for cancer prevention. CINJ’s physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. to make a tax-deductible gift to support CINJ, call 732-235-8614 or visit cinjfoundation.org. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

The CINJ Network is comprised of hospitals throughout the state and provides the highest quality cancer care and rapid dissemination of important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. system Partner: Meridian Cancer Care (Bayshore Community Hospital, Jersey Shore University Medical Center, Ocean Medical Center, Riverview Medical Center, and Southern Ocean Medical Center). Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon Cancer Center at Overlook Hospital, and Cooper University Hospital. Affiliate Hospitals: CentraState Healthcare system, JFK Medical Center, Mountainside Hospital, Raritan Bay Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), Somerset Medical Center, the University Hospital/UMDNJ-New Jersey Medical School*, and University Medical Center at Princeton. *Academic Affiliate

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In recent years, we've been bombarded with studies about the hormone oxytocin – researchers have demonstrated it increases trust and helps aid in social bonding. It has even garnered a reputation as the "love hormone." But what good is it for? Despite all these findings, the hormone's medical use remains limited to obstetrics – it is used to induce labor and aid in breastfeeding.

But researchers are now trying to apply these findings, and are investigating oxytocin as a treatment for psychiatric illnesses. they say its unique ability to adjust our wiring could remedy symptoms of schizophrenia, post-traumatic stress disorder (PTSD) and anxiety, and improve social abilities among those with autism.

A number of oxytocin studies have even reached the stage of clinical trials – which test the effectiveness and safety of a substance before it can become an approved drug – with promising findings.

"the idea of augmenting … the way we connect to and with each other, would just be so helpful for so many people," said Dr. Kai MacDonald, an adjunct professor of psychiatry at the University of California, San Diego, who has studied oxytocin as a treatment for schizophrenia.

However, the results so far, while hopeful, have not been "earthshaking," MacDonald said.

There are hurdles to such research. because oxytocin is a large molecule, it doesn't cross from the bloodstream into the brain very easily. It is also rapidly degraded in both the stomach and the blood.

Also, researchers don't know how big doses need to be, or how frequently it should be given to have a meaningful impact, MacDonald told MyHealthNewsDaily. Figuring out such dosing can be difficult.

Still, "if we could do it with any degree of precision, that would be a lovely therapeutic venue," MacDonald said.

Oxytocin is a hormone released by the pituitary gland that affects both the body and the brain. in the human body, it facilitates contractions of the uterus during labor and helps release milk during breastfeeding.

The hormone affects social interactions in a number of mammals, from mice and moles to dogs and monkeys, MacDonald said. for example, studies have shown that mice given oxytocin will huddle together, and monkeys given the hormone will spend longer grooming each other.

A barrage of studies over the last decade has indicated it has social effects on people as well.

One study found a nasal spray of oxytocin – a frequently used way to deliver the hormone, because it provides a direct route to the brain – made people more trusting. Participants were more willing to hand over money in an experimental game than those not given the spray.

Other researchers gave men oxytocin and found they more frequently looked to the eye region when shown pictures of human faces. People look to the eyes to read another's emotional state and trustworthiness, MacDonald said. [Related: 11 Interesting Effects of Oxytocin]

It's not clear that people who take oxytocin feel any different, MacDonald said. It may be that it acts subtly to change behavior or how we process social information, he said.

Though you can buy the hormone on websites that sell what they claim is an oxytocin nasal spray, whether it actually works is a different story. the claims need scientific scrutiny, a process still in its infancy, MacDonald said.

Oxytocin has not been approved to treat any psychiatric disorder, but evidence that it may be effective is building.

A small study published Oct. 1 in the journal Biological Psychiatry found that patients with schizophrenia who took oxytocin for three weeks along with their regular antipsychotic medication improved in their symptoms and hallucinated less than those who took a placebo with their antipsychotic.

While there were only 15 patients and the findings are preliminary, the results suggest oxytocin could treat patients with schizophrenia whose symptoms are not fully alleviated by their antipsychotics, said study researcher David Feifel, also of UCSD.

"the field of treating schizophrenia is kind of at an impasse," Feifel told MyHealthNewsDaily. "all our drugs that we have to date work through the same mechanisms as they did when antipsychotic drugs were first discovered 50 years ago," he said. "we are in desperate need of novel mechanisms that will improve symptoms through a different pathway, and oxytocin clearly is a novel mechanism."

Considering oxytocin's social effects, it makes sense to hypothesize it could treat autism, a condition characterized by having trouble interacting with others. And researchers have shown people with autism naturally have lower levels of oxytocin than those without autism.

A study published in 2007 in Biological Psychiatry found people with autism given oxytocin were able to determine the emotional tone of speech more consistently than those given a placebo.

Studies on other disorders have shown more mixed results. A paper published last year in the journal Psychoneuroendocrinology involving patients with social anxiety disorder found that oxytocin improved participants' self-image when they gave a speech. however, after five weeks of treatment, which also included teaching the patients to confront their social fears, those given oxytocin did no better than patients given the placebo.

Oxytocin is also being tested in clinical trials as a treatment for depression, borderline personality disorder and alcohol withdrawal.

How does oxytocin work?

One hypothesis is that oxytocin dampens the activity of the brain's fear center, the amygdala, thereby easing stress and anxiety.

A decline in anxiety could "allow people to attend to the social cues maybe they normally would avoid," said Jennifer Bartz, a professor of psychiatry at Mount Sinai School of Medicine in New York, who is conducting a clinical trial testing oxytocin as a therapy for autism. There is evidence people with autism experience anxiety in social situations, she said.

Because of oxytocin's proposed blunting effects on the amygdala's activity, scientists have also hypothesized it would help those with PTSD, which is a disorder of fear, said Miranda Olff, head of the Center for Psychological Trauma at the University of Amsterdam in the Netherlands. in PTSD, the brain "still gives the fear response as if people are back in that situation again," she said.

Olff is testing oxytocin's use in patients with PTSD in addition to standard therapies.

"Adding another biological component to this intervention might speed up recovery, or might increase the number of patients that respond to treatment at all," Olff said.

And oxytocin's trust effect could help those with schizophrenia, making them less paranoid, Feifel said.

Scientists don't know how much oxytocin goes into the brain when it is administered as a spray, or whether it even gets there, Feifel said. There is no way to see the hormone in the brain. But the effects it produces – such as a reduction in hallucinations – would require brain changes, so researchers have reason to believe it reaches the brain, he said.

It's also possible that an oxytocin dose simply triggers the brain to make more of it, MacDonald said.

Future research

While oxytocin's effects so far have been subtle rather than drastic, it could still become an important therapy. MacDonald said that most studies have looked at effects on patients after only a single dose. If Prozac, the widely-prescribed antidepressant, were administered that way, its effects would seem more subtle as well, he said.

The side effects of oxytocin have so far been benign, MacDonald said. But while it's something the body produces naturally, researchers don't know whether upping the body's natural amount, or giving it over long periods of time, could ultimately be harmful.

It also remains to be seen whether oxytocin affects men and women differently. It may present health risks to women because of its role in birth – inducing contractions of the uterus. Most studies to date have been conducted in men.

Besides mental disorders, researchers are investigating oxytocin's potential benefit for a number of other ailments, including headaches, constipation and skin damage.

For those who think they might benefit from an oxytocin boost, MacDonald noted that you don't need a spray to prompt the hormone's production."Given that some of the things that are suspected of triggering oxytocin – massage, sex, touch, eye contact – given that those are uniformly likable, it's hard not to recommend them," he said.

• 11 Interesting Effects of Oxytocin
• Mental Disorders Strike 1 in 5 Adults, Survey Finds
• Love Hormone could help Shy People Blossom

Follow MyHealthNewsDaily staff writer Rachael Rettner on Twitter @Rachael_MHND.

• Original story: Could 'love Hormone' Oxytocin Cure our Ills?

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