Posts Tagged ‘pancreatic-cancer’

Chemoprevention Gene Therapy Technique May Lead to Pancreatic Cancer Treatment

Chemoprevention Gene Therapy Technique May Lead to Pancreatic Cancer Treatment

Chemoprevention Gene Therapy Technique May Lead to Pancreatic Cancer Treatment

Researchers at the Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine have published findings that implicate a new chemoprevention gene therapy (CGT) for preventing and treating pancreatic cancer, one of the most lethal and treatment-resistant forms of cancer.

In the July issue of Molecular Cancer Therapeutics, the researchers showed that combining a dietary agent with a gene-delivered cytokine effectively eliminates human pancreatic cancer cells in mice displaying sensitivity to these highly aggressive and lethal cancer cells.

Cytokines are a category of proteins that are secreted into the circulation and can affect cancer cells at distant sites in the body, including metatases. The cytokine used in this study was melanoma differentiation associated gene-7/interleukin-24, known as mda-7/IL-24.

The dietary agent, perillyl alcohol (POH), was combined with mda-7/IL-24, which is already used in other cancer treatments. POH is found in a variety of plants, including citrus plants, and has been well-tolerated by patients who have received it in clinical studies.

The results indicated that the CGT approach not only prevented pancreatic cancer growth and progression, but it also effectively killed established tumors, thereby displaying profound chemopreventive and therapeutic activity.

Paul B. Fisher, Ph.D., was principal investigator of the study, which was supported by the National Institutes of Health and the Samuel Waxman Cancer Foundation. Fisher, who recently joined VCU from Columbia University, is professor and interim chair of VCU’s department of human and molecular genetics; holds the Thelma Newmeyer Corman chair in cancer research at Massey; and is director of the VCU Institute of Molecular Medicine.

“Our hypothesis was that certain non-toxic dietary agents that had the ability to promote reactive oxygen species (ROS) would break down pancreatic cancer cell resistance to therapy following administration of mda-7/IL-24 and be safe for human use,” said Fisher. “We are very excited at the prospect of this chemoprevention gene therapy as a means of both preventing and treating pancreatic cancer, and it has significant potential to move rapidly into human clinical trials.”

Pancreatic cancer has a five-year survival rate of less than 5 percent, and currently there is no effective chemotherapy or radiation therapy for it. About 37,000 new cases are diagnosed in the United States each year.

To read an abstract of the study, visit http://mct.aacrjournals.org/cgi/content/abstract/7/7/2042.

About the VCU Massey Cancer Center

VCU Massey Cancer Center is one of only 66 National Cancer Institute-designated institutions in the country that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers a wide range of clinical trials throughout Virginia, oftentimes the most trials in the state, and serves patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at www.massey.vcu.edu or call 877-4-MASSEY for more information.

About VCU and the VCU Medical Center

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 222 degree and certificate programs in the arts, sciences and humanities. Sixty-six of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.

Researchers at the Virginia Commonwealth University might have come upon a method that will effectively address pancreatic cancer, one of the most pernicious diseases having no real treatment options.

In the July issue of Molecular Cancer Therapeutics, the researchers showed that combining a dietary agent with a gene-delivered cytokine effectively eliminates human pancreatic cancer cells in mice displaying sensitivity to these highly aggressive and lethal cancer cells.

Cytokines are a category of proteins that are secreted into the circulation and can affect cancer cells at distant sites in the body, including metatases. The cytokine used in this study was melanoma differentiation associated gene-7/interleukin-24, known as mda-7/IL-24.

The dietary agent, perillyl alcohol (POH), was combined with mda-7/IL-24, which is already used in other cancer treatments. POH is found in a variety of plants, including citrus plants, and has been well-tolerated by patients who have received it in clinical studies.

The results indicated that the CGT approach not only prevented pancreatic cancer growth and progression, but it also effectively killed established tumors, thereby displaying profound chemopreventive and therapeutic activity.

Source : http://www.news.vcu.edu/news/VCU_Massey_Cancer_Center_and_VCU_Institute_of_Molecular_Medicine

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KSU creates simple blood test that can accurately detect lung and breast cancer’s early stages

KSU creates simple blood test that can accurately detect lung and breast cancer’s early stages

Researchers at Kansas State University have developed a simple blood test that can accurately detect the beginning stages of cancer.

In less than an hour, the test can detect breast cancer and non-small lung cancer — the most common type of lung cancer — before symptoms like coughing and weight loss start. The researchers anticipate testing for the early stages of pancreatic cancer shortly.

The test was developed by Stefan Bossmann, professor of chemistry, and Deryl Troyer, professor of anatomy and physiology. Both are also researchers affiliated with Kansas State University’s Johnson Cancer Research Center and the University of Kansas Cancer Center. Gary Gadbury, professor of statistics at Kansas State University, helped analyze the data from tests with lung and breast cancer patients. The results, data and analysis were recently submitted to the Kansas Bio Authority for accelerated testing.

“We see this as the first step into a new arena of investigation that could eventually lead to improved early detection of human cancers,” Troyer said. “Right now the people who could benefit the most are those classified as at-risk for cancer, such as heavy smokers and people who have a family history of cancer. The idea is these at-risk groups could go to their physician’s office quarterly or once a year, take an easy-to-do, noninvasive test, and be told early on whether cancer has possibly developed.”

The researchers say the test would be repeated a short time later. If cancer is confirmed, diagnostic imaging could begin that would otherwise not be routinely pursued.

According to the American Cancer Society, an estimated 39,920 breast cancer deaths and 160,340 lung cancer deaths are expected in the U.S. in 2012.

With the exception of breast cancer, most types of cancer can be categorized in four stages based on tumor growth and the spread of cancer cells throughout the body. Breast and lung cancer are typically found and diagnosed in stage 2, the stage when people often begin exhibiting symptoms such as pain, fatigue and coughing. Numerous studies show that the earlier cancer is detected, the greater chance a person has against the disease.

“The problem, though, is that nobody knows they’re in stage 1,” Bossmann said. “There is often not a red flag to warn that something is wrong. Meanwhile, the person is losing critical time.”

The test developed by Kansas State University’s Bossmann and Troyer works by detecting increased enzyme activity in the body. Iron nanoparticles coated with amino acids and a dye are introduced to small amounts of blood or urine from a patient. The amino acids and dye interact with enzymes in the patient’s urine or blood sample. Each type of cancer produces a specific enzyme pattern, or signature, that can be identified by doctors.

“These enzyme patterns can also help distinguish between cancer and an infection or other diseases that commonly occur in the human body,” Bossmann said. “For example, a person who smokes a lot of cigars may develop an inflammation in their lungs. That will drive up some of the markers in the test but not all of them. Doctors will be able to see whether there was too much smoke inhalation or if there is something more serious going on. False-positives are something that we really want to avoid.”

Once the test is administered, comprehensive results — which include enzyme patterns — are produced in roughly 60 minutes.

Bossmann and Troyer have designed a second testing method that is anticipated to produce the same results in about five minutes. The team recently received $305,000 in funding for this project from the National Science Foundation’s Division of Chemical, Bioengineering, Environmental and Transport Systems.

In addition to early detection, researchers say the test can be tweaked to monitor cancer. For example, patients being treated with drugs can be observed for drug effectiveness. Similarly, doctors can use the dye in the test to determine if the entirety of a tumor has been successfully removed from a patient after surgery.

Researchers evaluated the test’s accuracy on 32 separate participants in various stages of breast or lung cancer. Data was collected from 20 people with breast cancer — ranging in age from 36 to 81 years old — and 12 people with lung cancer — ranging in age from 27 to 63 years old.

Twelve people without cancer were also tested as a control group. This group ranged in age from 26 to 62 years old.

A blood sample from each participant was tested three times. Analysis of the data showed a 95 percent success rate in detecting cancer in participants, including those with breast cancer in stages 0 and 1 and those with lung cancer in stages 1 and 2.

Tests detecting for pancreatic cancer are anticipated to begin in October as part of Bossmann and Troyer’s collaboration with Dr. Stephen Williamson at the University of Kansas Medical Center. Blood samples from triple-negative breast cancer patients will be tested this fall in collaboration with Dr. Priyanka Sharma, who is also at the University of Kansas Medical Center.

Source : http://www.news-medical.net/news/20120927/KSU-creates-simple-blood-test-that-can-accurately-detect-lung-and-breast-cancere28099s-early-stages.aspx

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KSU creates simple blood test that can accurately detect lung and breast cancer’s early stages

KSU creates simple blood test that can accurately detect lung and breast cancer’s early stages

Researchers at Kansas State University have developed a simple blood test that can accurately detect the beginning stages of cancer.

In less than an hour, the test can detect breast cancer and non-small lung cancer — the most common type of lung cancer — before symptoms like coughing and weight loss start. The researchers anticipate testing for the early stages of pancreatic cancer shortly.

The test was developed by Stefan Bossmann, professor of chemistry, and Deryl Troyer, professor of anatomy and physiology. Both are also researchers affiliated with Kansas State University’s Johnson Cancer Research Center and the University of Kansas Cancer Center. Gary Gadbury, professor of statistics at Kansas State University, helped analyze the data from tests with lung and breast cancer patients. The results, data and analysis were recently submitted to the Kansas Bio Authority for accelerated testing.

“We see this as the first step into a new arena of investigation that could eventually lead to improved early detection of human cancers,” Troyer said. “Right now the people who could benefit the most are those classified as at-risk for cancer, such as heavy smokers and people who have a family history of cancer. The idea is these at-risk groups could go to their physician’s office quarterly or once a year, take an easy-to-do, noninvasive test, and be told early on whether cancer has possibly developed.”

The researchers say the test would be repeated a short time later. If cancer is confirmed, diagnostic imaging could begin that would otherwise not be routinely pursued.

According to the American Cancer Society, an estimated 39,920 breast cancer deaths and 160,340 lung cancer deaths are expected in the U.S. in 2012.

With the exception of breast cancer, most types of cancer can be categorized in four stages based on tumor growth and the spread of cancer cells throughout the body. Breast and lung cancer are typically found and diagnosed in stage 2, the stage when people often begin exhibiting symptoms such as pain, fatigue and coughing. Numerous studies show that the earlier cancer is detected, the greater chance a person has against the disease.

“The problem, though, is that nobody knows they’re in stage 1,” Bossmann said. “There is often not a red flag to warn that something is wrong. Meanwhile, the person is losing critical time.”

The test developed by Kansas State University’s Bossmann and Troyer works by detecting increased enzyme activity in the body. Iron nanoparticles coated with amino acids and a dye are introduced to small amounts of blood or urine from a patient. The amino acids and dye interact with enzymes in the patient’s urine or blood sample. Each type of cancer produces a specific enzyme pattern, or signature, that can be identified by doctors.

“These enzyme patterns can also help distinguish between cancer and an infection or other diseases that commonly occur in the human body,” Bossmann said. “For example, a person who smokes a lot of cigars may develop an inflammation in their lungs. That will drive up some of the markers in the test but not all of them. Doctors will be able to see whether there was too much smoke inhalation or if there is something more serious going on. False-positives are something that we really want to avoid.”

Once the test is administered, comprehensive results — which include enzyme patterns — are produced in roughly 60 minutes.

Bossmann and Troyer have designed a second testing method that is anticipated to produce the same results in about five minutes. The team recently received $305,000 in funding for this project from the National Science Foundation’s Division of Chemical, Bioengineering, Environmental and Transport Systems.

In addition to early detection, researchers say the test can be tweaked to monitor cancer. For example, patients being treated with drugs can be observed for drug effectiveness. Similarly, doctors can use the dye in the test to determine if the entirety of a tumor has been successfully removed from a patient after surgery.

Researchers evaluated the test’s accuracy on 32 separate participants in various stages of breast or lung cancer. Data was collected from 20 people with breast cancer — ranging in age from 36 to 81 years old — and 12 people with lung cancer — ranging in age from 27 to 63 years old.

Twelve people without cancer were also tested as a control group. This group ranged in age from 26 to 62 years old.

A blood sample from each participant was tested three times. Analysis of the data showed a 95 percent success rate in detecting cancer in participants, including those with breast cancer in stages 0 and 1 and those with lung cancer in stages 1 and 2.

Tests detecting for pancreatic cancer are anticipated to begin in October as part of Bossmann and Troyer’s collaboration with Dr. Stephen Williamson at the University of Kansas Medical Center. Blood samples from triple-negative breast cancer patients will be tested this fall in collaboration with Dr. Priyanka Sharma, who is also at the University of Kansas Medical Center.

Source : http://www.news-medical.net/news/20120927/KSU-creates-simple-blood-test-that-can-accurately-detect-lung-and-breast-cancere28099s-early-stages.aspx

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RNA-delivering nanoparticles allow rapid screening of new drug targets in mice

RNA-delivering nanoparticles allow rapid screening of new drug targets in mice

By sequencing cancer-cell genomes, scientists have discovered vast numbers of genes that are mutated, deleted or copied in cancer cells. This treasure trove is a boon for researchers seeking new drug targets, but it is nearly impossible to test them all in a timely fashion.

To help speed up the process, MIT researchers have developed RNA-delivering nanoparticles that allow for rapid screening of new drug targets in mice. In their first mouse study, done with researchers at Dana-Farber Cancer Institute and the Broad Institute, they showed that nanoparticles that target a protein known as ID4 can shrink ovarian tumors.

The nanoparticle system, described in the Aug. 15 online edition of Science Translational Medicine, could relieve a significant bottleneck in cancer-drug development, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of the David H. Koch Institute for Integrative Cancer Research at MIT.

“What we did was try to set forth a pipeline where you start with all of the targets that are pouring out of genomics, and you sequentially filter them through a mouse model to figure out which ones are important. By doing that, you can prioritize the ones you want to target clinically using RNA interference, or develop drugs against,” says Bhatia, one of the paper’s senior authors.

William Hahn, an associate professor of medicine at Harvard Medical School and the paper’s other senior author, is the leader of Project Achilles, a collaborative effort to identify promising new targets for cancer drugs from the flood of data coming from the National Cancer Institute’s cancer-genome-sequencing project.

Among those potential targets are many considered to be “undruggable,” meaning that the proteins don’t have any pockets where a traditional drug could bind to them. The new nanoparticles, which deliver short strands of RNA that can shut off a particular gene, may help scientists go after those undruggable proteins.

“If we could figure out how to make this work [in humans], it would open up a whole new class of targets that hadn’t been available,” says Hahn, who is also director of the Center for Cancer Genome Discovery at Dana-Farber and a senior associate member of the Broad Institute.

Lead authors of the paper are Yin Ren, an MD/PhD student in Bhatia’s lab, and Hiu Wing Cheung, a postdoc in Hahn’s lab.

An abundance of targets

Through Project Achilles, Hahn and his colleagues have been testing the functions of many of the genes disrupted in ovarian cancer cells. By revealing genes critical to cancer-cell survival, this approach has narrowed the list of potential targets to several dozen.

Typically, the next step in identifying a good drug target would be to genetically engineer a strain of mice that are missing (or overexpressing) the gene in question, to see how they respond when tumors develop. However, this normally takes two to four years. A much faster way to study these genes would be simply to turn them off after a tumor appears.

RNA interference (RNAi) offers a promising way to do that. During this naturally occurring phenomenon, short strands of RNA bind to the messenger RNA (mRNA) that delivers protein-building instructions from the cell’s nucleus to the rest of the cell. Once bound, the mRNA molecules are destroyed and their corresponding proteins never get made.

Scientists have been pursuing RNAi as a cancer treatment since its discovery in the late 1990s, but have had trouble finding a way to safely and effectively target tumors with this therapy. Of particular difficulty was finding a way to get RNA to penetrate tumors.

Bhatia’s lab, which has been working on RNAi delivery for several years, joined forces with Hahn’s group to identify and test new drug targets. Their goal was to create a “mix and dose” technique that would allow researchers to mix up RNA-delivery particles that target a particular gene, inject them into mice and see what happens.

Shrinking tumors

In their first effort, the researchers decided to focus on the ID4 protein because it is overexpressed in about a third of high-grade ovarian tumors (the most aggressive kind), but not in other cancer types. The gene, which codes for a transcription factor, appears to be involved in embryonic development: It gets shut down early in life, then somehow reactivates in ovarian tumors.

To target ID4, Bhatia and her students designed a new type of RNA-delivering nanoparticle. Their particles can both target and penetrate tumors, something that had never before been achieved with RNA interference.

On their surface, the particles are tagged with a short protein fragment that allows them to enter tumor cells. Those fragments are also drawn to a protein found on tumor cells, known as p32. This fragment and many similar ones were discovered by Erkki Ruoslahti, a professor at the Sanford-Burnham Medical Research Institute at the University of California at Santa Barbara, who is also an author of the new paper.

Within the nanoparticles, strands of RNA are mixed with a protein that further helps them along their journey: When the particles enter a cell, they are encapsulated in membranes known as endosomes. The protein-RNA mixture can cross the endosomal membrane, allowing the particles to get into the cell’s main compartment and start breaking down mRNA.

In a study of mice with ovarian tumors, the researchers found that treatment with the RNAi nanoparticles eliminated most of the tumors.

The researchers are now using the particles to test other potential targets for ovarian cancer as well as other types of cancer, including pancreatic cancer. They are also looking into the possibility of developing the ID4-targeting particles as a treatment for ovarian cancer.

Source : http://www.news-medical.net/news/20120816/RNA-delivering-nanoparticles-allow-rapid-screening-of-new-drug-targets-in-mice.aspx

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Afinitor (Everolimus) For Rare Pancreatic Cancer Approved By FDA

Afinitor (Everolimus) For Rare Pancreatic Cancer Approved By FDA

"Patients with this cancer have few effective treatment options. Afinitor has demonstrated the ability to slow the growth and spread of neuroendocrine tumors of the pancreas."

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