Device delivers toxic chemo cocktail to pancan tumor, spares body

Researchers have found a way to hit pancreatic cancer hard with a drug-delivery device that puts a lethal combination of four chemo drugs directly into the tumor while limiting the impact on the rest of the body.

Pancreatic cancer is a killer, and to attack a killer you sometimes need to hit it with a highly toxic drug cocktail. However, doing this through the bloodstream only works in a few patients because of the widespread damage to the rest of the body.

In the Proceedings of the National Academy of Sciences, the team from the University of North Carolina (UNC) at Chapel Hill describes how they tested the implantable “iontophoretic device” in mice.

The researchers found that using the iontophoretic device to deliver a particularly toxic mix of four chemotherapy drugs stopped pancreatic tumors in the mice from growing – and in some cases even shrank them – while sparing the rest of the body.

Senior author Jen Jen Yeh, an associate professor of surgery and pharmacology in the UNC School of Medicine, says:

“It’s an exciting approach because there is so little systemic toxicity that it leaves room to administer additional drugs against cancer cells that may have spread in the rest of the body.”

In their study, the team found that compared with intravenous delivery, the iontophoretic device “resulted in better tumor response and tolerability,” when used to attack pancreatic tumors in mice with FOLFIRINOX – a combination of the chemotherapy drugs folinic acid (leucovorin), fluorouracil, irinotecan and oxaliplatin.

Helping more patients qualify for surgery

FOLFIRINOX is a first-line treatment for pancreatic cancer and has been shown to halt or shrink tumors in nearly a third of patients. However, because it is so toxic to the rest of the body, there are many patients who cannot tolerate it when it is delivered through the bloodstream.

The implantable device uses an electric field to drive the chemotherapy drugs directly into the tumor.

The new study follows another published a year ago where the team showed the first successful use of the iontophoretic device in treating human pancreatic tumors grafted into mice and dogs.

Pancreatic cancer is the cause of 7% of all cancer deaths and ranks fourth as a cause of cancer death in both men and women every year in the US, where rates of the disease have been rising by 1.2% a year over the last 10 years.

Early stage pancreatic cancer usually has no symptoms and spreads quickly to the rest of the body, making it difficult to detect and harder to treat when it is found in its later stages.

Consequently, only one in four patients survive more than a year after diagnosis – a statistic that has not changed in over 40 years.

Surgery to remove the pancreatic tumor is currently the best chance of cure, but unfortunately only 15% of patients have operable tumors.

The hope is that the new device will halt and potentially shrink tumors so that more patients with localized and locally advanced pancreatic cancer qualify for surgery.

The team is planning to get the device into clinical trials in the next few years.

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*credit verbatim via Catharine Paddock PhD and http://www.medicalnewstoday.com *

Costa Rican Receives Patent For Pancreatic Cancer Vaccine

Christian Marin-Muller, molecular biologist and business manager with a PhD in molecular virology, is the 33 year old Costa Rican that has what few scientists achieve in life: a patent for a vaccine.

From his laboratory at Baylor College of Medecine in Texas, Marín paved the way for a vaccine against pancreatic cancer.

The vaccine is not preventive, rather it is a therapeutic vaccine that is applied in order to reduce or control the tumor.

Working on the vaccine with Marin-Muller were Qizhi Yao and Changyi Chen .

The key to stop the growth and spread of pancreatic cancer could be found in a microRNA called MiR-198, said researchers at Baylor College of Medicine in a report that appears online in the journal Clinical Cancer Research.

Their findings reveal a treatment target that, when modulated in the lab setting, reduces tumors and makes them more susceptible to chemotherapy.

Before this vaccine is approved, it requires human clinical trials.

Clinical trials have three phases: in the first the safety of the vaccine (side effects) is tested, in the second efficacy ( as served) and the third will confirm the two previous phases.

This process takes about 10 years, but being that pancreatic cancer is a very aggressive cancer for which no treatment is accurate, it could take only three years.

The process is expensive , costing about US$ 1 billion.

However, Marin told La Nacion in an interview, he is hopeful that there are companies interested and materialize his dream of helping in the treatment of one of the most aggressive and deadly tumors.

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*credit verbatim via http://qcostarica.com and Rico*

Pancreatic cancer may be treatable with tree extract

With no effective treatments currently available, there is an urgent and important need to develop new drugs to treat pancreatic cancer. After carrying out tests in lab cells and mice, researchers propose that nimbolide, a natural extract from the leaves of the neem tree, could meet such a need.

In the journal Scientific Reports, a team of biomedical scientists at Texas Tech University Health Sciences Center El Paso (TTUHSC El Paso) reports how nimbolide can stop pancreatic cancer growing and spreading without harming normal, healthy cells.

Senior and corresponding author Rajkumar Lakshmanaswamy, an associate professor in TTUHSC El Paso’s Center of Emphasis in Cancer, says:

“The promise nimbolide has shown is amazing, and the specificity of the treatment towards cancer cells over normal cells is very intriguing.”

Pancreatic cancer is the fourth leading cause of cancer-related death in the US and is projected to become the second leading cause by 2020. It is the only major cancer, note the authors, where fewer than 6 out of every 100 patients survive more than 5 years after diagnosis.

The main reason pancreatic cancer is so deadly is because it is very difficult to diagnose in the early stages, before it has started to spread and invade surrounding tissue and other organs, which it does very fast.

Consequently, most patients with pancreatic cancer are diagnosed when the disease is in an advanced stage. For them, surgery is rarely an option, underscoring the importance of finding new therapies.

Nimbolide boosts production of reactive oxygen species:

Nimbolide is a natural extract derived from the leaves and flowers of the neem tree (Azadirachta indica) that is widely used in traditional medicine to treat a variety of human ailments.

Previous studies of nimbolide’s effect in lab cells and animals reveal that nimbolide has a number of anti-cancer properties. The compound interferes with cancer cell signaling pathways that are linked to inflammation, survival, growth, invasion, development of tumor blood vessels and cancer spread, or metastasis.

The new study, which tests nimbolide specifically on pancreatic cancer cell lines and mice, finds the compound is effective in inhibiting cancer growth and metastasis.

The researchers found that nimbolide boosts the production of a group of molecules known as reactive oxygen species (ROS), which is known to regulate cell death by apoptosis (self-killing) and autophagy (self-eating).

Further experiments in the pancreatic cancer cell lines revealed that ROS generation by nimbolide curbed proliferation of cells and reduced their ability to migrate, invade and form colonies.

However, the authors note that an area that needs to be researched further is the complex interplay between apoptosis and autophagy resulting from the nimbolide-induced boost in ROS. In this study, the anti-cancer effect of nimbolide seems to be via apoptosis, and not via autophagy, which other studies suggest may actually increase cancer cell survival.

Nimbolide ‘attacks pancreatic cancer from all angles’:

The results show that nimbolide reduced the size and number of pancreatic cancer cell colonies by 80% and curbed their migration and invasion capabilities by 70%.

Experiments in live mice also showed that nimbolide is effective in inhibiting pancreatic cancer growth and metastasis, note the authors.

“Nimbolide seems to attack pancreatic cancer from all angles,” says Prof. Lakshmanaswamy.

An important finding of the study is that nimbolide did not appear to harm healthy cells – either in the lab cultures or in the live mice.

As many people in India eat neem and do not appear to experience harmful side effects, the authors suggest using nimbolide for pancreatic cancer would be unlikely to produce the side effects typically seen with chemotherapy and radiation therapy.

However, while this fact and the study findings all sound promising, Prof. Lakshmanaswamy points out there is still a long way to go before nimbolide is ready for treating pancreatic cancer in humans.

The team is continuing their research into the anti-cancer properties of nimbolide and also plans to investigate how best to administer it to maximize its effect on pancreatic cancer.

Meanwhile, Medical News Today recently learned how researchers have found a way to hit pancreatic cancer hard with a device that uses an electric field to drive a deadly combination of four chemo drugs directly into the tumor while limiting side effects to the rest of the body.

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*credit verbatim via http://www.medicalnewstoday.com and Catharine Paddock PhD*

How certain drugs alter metabolism of pancreatic cancer cells

UT Southwestern Medical Center researchers have found that cancer drugs known as CDK4/6-inhibitors alter the metabolism of pancreatic cancer cells, revealing a biologic vulnerability that could be exploited for therapeutic gain. The findings were published today in Cell Reports.

Because pancreatic cancer has one of the worse prognoses of any cancer and is the third leading cause of cancer deaths in the U.S., according to the National Cancer Institute, researchers for years have sought to find better treatment options.

Last year, the FDA approved the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for treating a certain type of advanced breast cancer. This class of drugs has been widely studied in clinical trials for many other types of cancer, including pancreatic cancer. CDK 4/6 inhibitors are cytostatic, meaning they work by preventing cancer cells from growing and dividing.

“On the one hand, that’s great, because the tumor won’t grow, but on the other hand, the patient still has a tumor, which will eventually become resistant to those drugs,” said study senior author Dr. Erik Knudsen, Professor of Internal Medicine in the Eugene McDermott Center for Human Growth and Development at UT Southwestern.

“There’s a lot of interest in better understanding the biology behind CDK4/6 inhibitors — and in finding out whether we can use that information to kill tumors instead of simply stopping their growth,” added Dr. Agnieszka Witkiewicz, also in the McDermott Center and an Associate Professor of Pathology.

In this study, the research team treated human pancreatic cancer cells and tumors grown in mice with CDK4/6-inhibiting drugs. Surprisingly, they found that when tumor cells were treated with CDK4/6 inhibitors, the cells’ metabolism — the way cancer tumors get energy — became more active.

“Now we can try attacking specific aspects of CDK4/6-induced metabolic programming,” said Dr. Knudsen, also a member of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, along with Dr. Witkiewicz. “For example, by targeting altered tumor metabolism, we could potentially turn the cytostatic effect of CDK4/6 inhibitors into a cytotoxic effect that actually kills the cancer cells.”

The upshot is that by disrupting a tumor’s cell cycle with CDK4/6 inhibitors and then targeting the altered metabolism with other drugs — such as mTOR inhibitors — it may be possible to positively impact cancer treatment.

“These data yield valuable new insights into the cross talk between CDK inhibitors, signaling pathways, and tumor metabolism in pancreatic cancer, opening up some interesting new possibilities for treatment that could be evaluated in clinical trials,” Dr. Witkiewicz said. “The real goal is that this work — as well as ongoing studies — will benefit patients with pancreatic cancer.”

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*credit verbatim via http://www.sciencedaily.com provided by UT Southwestern Medical Center

 

Scientists discover how diabetes drug Metformin slows down pancreatic cancer

Researchers at the Massachusetts General Hospital (MGH) might have stumbled upon the mechanism of how the diabetes drug metformin can slow down the progression of cancer of the pancreas.

The details of the study are published in the journal PLOS One, where the team describes that this common diabetes drug decreases the inflammation and fibrosis seen commonly in pancreatic cancer. However, based on their findings in patient tumor samples as well as cellular and animal models, the researchers add that in overweight and obese patients might benefit more from this surprising metformin discovery.

The study focused on the most commonly occuring pancreatic cancer – pancreatic ductal adenocarcinoma (PDA) – which kills almost 40,000 people in the U.S. ever year. Half of those diagnosed with PDA are overweight or obese, and almost 80 percent are insulin resistant or have type 2 diabetes.

Previous analyses have revealed that Diabetic patients taking metformin have a lower risk of developing PDA; and those who do have PDA have a reduced fatality rate. But before the current study nobody knew how or why this drug inhibited the progress of pancreatic cancer.

The team discovered that metformin increases a collection of tumor-associated immune cells and a dense connective tissue which are both characteristic of pancreatic cancer. According to the lead author of the study, Dai Fukumura, MD, PhD, of the Steele Laboratory of Tumor Biology in the MGH Department of Radiation Oncology, metformin does this by slowing down the activation of the pancreatic stellate cells (cells that cause fibrosis and interact closely with cancer cells to create a tumor friendly environment) and by reprogramming immune cells to reduce inflammation.

However the team observed that hat these changes were more pronounced in the tumors of obese and overweight individuals, in whom the tumors had increased fibrosis.

In fat mice, the researchers found that metformin treatment reduced levels of tumor-associated macrophages by 60 percent. The tumors of animals treated with metformin also had showed a reduction in metastasis, suggesting a lower risk in the spread of the cancer.

This new evidence is part of a wave of findings that suggest that regular everyday drugs can play a huge role in preventing and fighting cancer. In fact an organization called ReDo has been set up solely for this purpose of finding regular drugs with anti-cancer properties.

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*credit verbatim via http://www.belmarrahealth.com and Mohan Garikiparithi*

Merck, BioLineRX to study drug combo to fight #PancreaticCancer

Israeli biopharmaceutical company BioLineRX Ltd said on Tuesday it would collaborate with U.S. industry heavyweight Merck to test a combination of drugs for the treatment of pancreatic cancer.

The companies will partner in a mid-stage study to evaluate the safety and efficacy of the combination of BioLineRx’s BL-8040 and Merck’s Keytruda in patients with metastatic pancreatic adenocarcinoma.

“Because certain tumors exhibit only a modest response to existing immunotherapies, we are increasingly seeing clinical studies involving combinations of immuno-oncology agents with other classes of drugs,” said Kinneret Savitsky, BioLineRx’s chief executive.

BL-8040 acts against CXCR4 receptors that are involved in tumor progression, the company said. It has been shown in several clinical trials to mobilize immune cells and to be effective at inducing direct tumor cell death.

Keytruda, an antibody, works by increasing the ability of the body’s immune system to help detect and fight tumor cells, said Merck, which is known as MSD outside the United States and Canada.

Pancreatic adenocarcinoma accounts for most cases of pancreatic cancer, according to the American Cancer Society. Specific symptoms often do not develop until the disease has reached an advanced stage, which is reflected in a low five-year survival rate.

The study is due to start by mid-2016 and both companies will have the option to expand the collaboration to include a pivotal registration study, BioLineRX said.

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*credit verbatim via http://www.channelnewsasia.com , Ari Rabinovitch, reporter; David Clarke, editing*

 

 

More magnesium may lower risk of pancreatic cancer

Magnesium intake may be an effective way to prevent pancreatic cancer, a new study suggests.

Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women in the United States. The overall occurrence of pancreatic cancer has not significantly changed since 2002, but the mortality rate has increased annually from 2002 to 2011, according to the National Cancer Institute.

“Pancreatic cancer is really unique and different from other cancers,” says Ka He, chair of the epidemiology and biostatistics department at Indiana University. “The five-year survival rate is really low, so that makes prevention and identifying risk factors or predictors associated with pancreatic cancer very important.”

Previous studies have found that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. But few studies have explored the direct association of magnesium with pancreatic cancer and those that did had inconclusive findings, says lead author Daniel Dibaba, a PhD student in the School of Public Health.

Using information from the VITamins and Lifestyle study, the researchers analyzed an enormous trove of data on more than 66,000 men and women, ages 50 to 76, looking at the direct association between magnesium and pancreatic cancer and whether age, gender, body mass index, non-steroidal anti-inflammatory drugs use, and magnesium supplementation play a role.

Of those followed, 151 participants developed pancreatic cancer. Every 100-milligrams-per-day decrease in magnesium intake was associated with a 24 percent increase in the occurrence of pancreatic cancer.

The study, published in the British Journal of Cancer, also found that the effects of magnesium on pancreatic cancer did not appear to be modified by age, gender, body mass index, or non-steroidal anti-inflammatory drug use, but was limited to those taking magnesium supplements either from a multivitamin or individual supplement.

“For those at a higher risk of pancreatic cancer, adding a magnesium supplement to their diet may prove beneficial in preventing this disease,” Dibaba says.

“While more study is needed, the general population should strive to get the daily recommendations of magnesium through diet, such as dark, leafy greens or nuts, to prevent any risk of pancreatic cancer.”

Other researchers from Indiana University and from the University of Washington, and the Jikei University School of Medicine in Tokyo contributed to the study.

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* credit verbatim via http://www.futurity.org and
April Toler of Indiana University *