Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells

Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells

September 24, 2008

New 'suicide gene' delivery approach offers potential for novel therapy

PHILADELPHIA - A research team, led by investigators at the Department of Surgery at Jefferson Medical College of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, has achieved a substantial "kill" of pancreatic cancer cells by using nanoparticles to successfully deliver a deadly diphtheria toxin gene. The findings - set to be published in the October issue of Cancer Biology & Therapy - reflect the first time this unique strategy has been tested in pancreatic cancer cells, and the success seen offers promise for future pre-clinical animal studies, and possibly, a new clinical approach.




The researchers found that delivery of a diphtheria toxin gene inhibited a basic function of pancreatic tumor cells by over 95 percent, resulting in significant cell death of pancreatic cancer cells six days after a single treatment. They also demonstrated that the treatment targets only pancreatic cancer cells and leaves normal cells alone, thus providing a potential 'therapeutic window.' Further, they are targeting a molecule that is found in over three-quarters of pancreatic cancer patients.

"For the pancreatic cancer world, this is very exciting," says the study's lead author, molecular biologist Jonathan Brody, Ph.D., assistant professor, Department of Surgery at Jefferson Medical College of Thomas Jefferson University, who works closely with the Samuel D. Gross Professor and Surgeon, Charles J. Yeo, M.D. "There are no effective targeted treatments for pancreatic cancer, aside from surgery for which only a minority of patients qualify. We are in great need of translating the plethora of molecular information we know about this disease to novel therapeutic ideas."

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the U.S., reflecting the generally short survival time of patients - often less than a year from diagnosis.

This approach was originally developed in ovarian cancer cells by study co-author Janet Sawicki, Ph.D., a member of the Kimmel Cancer Center, and professor at the Lankenau Institute for Medical Research in Wynnewood, Pennsylvania. She and her group had recent success in reducing the size of ovarian tumors following treatment with diphtheria toxin nanoparticles.

The strategy is based on the fact that both ovarian and pancreatic cancer cells significantly over-express a protein found on the cell membrane, called mesothelin. The function of that molecule is unknown, but it is found in the majority of pancreatic tumors and ovarian cancer tumors. Other solid tumors also express mesothelin, but not at such a high rate.

"We don't know completely why cancer cells repeatedly turn on mesothelin genes to produce these membrane proteins, but it gives us a way to fool the cell and hijack its machinery, to trick it into making other more potent genes that will be detrimental to the cancer cells," Brody says.

To do that, the researchers devised an agent that consists of a bit of mesothelin DNA connected to the gene that produces the toxin from diphtheria, a highly contagious and potentially deadly bacteria, which is now controlled through childhood DPT vaccination. "Naked" DNA is then coated in a polymer to form nanoparticles that are taken up by the cancer cells.

Inside the cells, the agent performs its trickery. The nanoparticles biodegrade and the cell machinery senses genetic material from mesothelin. It activates the diphtheria toxin gene, which then turns on production of the toxin which allows the toxin to then do its work on the cancer cells, Brody says. Within 24 hours of delivery, the toxin disrupted production of protein machinery by over 95 percent, and within six days, a number of cancer cells die or are arrested.

"The cancer thinks it is turning on mesothelin and once it gets started reading that genetic code, it can't stop," he says. "So it will read the bacteria's DNA and produce the toxin which shuts down protein production in the cancer cells."

"It worked well in our cell culture models and now we are moving into pre-clinical experiments," Brody says.

The agent will not attack normal cells because the molecular machinery needed to turn on mesothelin is not found in normal cells, Brody says. Additionally, Sawicki has modified the diphtheria DNA to ensure that toxin that might be released from dying cancer cells is not taken up by healthy, normal cells.

But the researchers are now perfecting even more stringent measures to ensure safety, he says. "We can't help being hopeful," he says. "Our findings suggest that such a strategy will work in the clinical setting against the majority of pancreatic tumors."

Thomas Jefferson University



Related Pancreatic Cancer Current Events and Pancreatic Cancer News Articles Pancreatic Cancer Current Events and Pancreatic Cancer News RSS Pancreatic Cancer Current Events and Pancreatic Cancer News RSS
Stanford blood scanner detects even faint indicators of cancer
A team led by Stanford researchers has developed a prototype blood scanner that can find cancer markers in the bloodstream in early stages of the disease, potentially allowing for earlier treatment and dramatically improved chances of survival.

2 new compounds show promise for eliminating breast cancer tumors
Two new compounds created by a University of Central Florida professor show early promise for destroying breast cancer tumors.

The miseries of allergies just may help prevent some cancers, study finds
There may be a silver -- and healthy -- lining to the miserable cloud of allergy symptoms: Sneezing, coughing, tearing and itching just may help prevent cancer -- particularly colon, skin, bladder, mouth, throat, uterus and cervix, lung and gastrointestinal tract cancer, according to a new Cornell study.

Cancer drugs my build and not tear down blood vessels
Scientists have thought that one way to foil a tumor from generating blood vessels to feed its growth - a process called angiogenesis - was by creating drugs aimed at stopping a key vessel growth-promoting protein. But now the opposite seems to be true.

UC Davis researchers discover Achilles' heel in pancreatic cancer
UC Davis Cancer Center researchers have discovered a metabolic deficiency in pancreatic cancer cells that can be used to slow the progress of the deadliest of all cancers.

Jefferson Department of Surgery announces new pancreas tumor registry
Charles J. Yeo, M.D., Samuel D. Gross Professor and Chair, Department of Surgery at Jefferson Medical College of Thomas Jefferson University, announces the establishment of the new Jefferson Pancreas Tumor Registry (JPTR).

Supercomputer provides massive computational boost to biomedical research at TGen
In less time than the blink of an eye, the Translational Genomics Research Institute's new supercomputer at Arizona State University can do operations equal to every dollar in the recent Wall Street bailout.

Hepatitis B exposure may increase risk for pancreatic cancer
In a first-of-its-kind finding, researchers at The University of Texas M. D. Anderson Cancer Center have discovered that exposure to the hepatitis B virus (HBV) may increase the risk of pancreatic cancer.

Study finds association between hepatitis B and pancreatic cancer
A new study has shown that evidence of past hepatitis B infection was twice as common in people with pancreatic cancer than in healthy controls. This study is the first to report an association between past exposure to the hepatitis B virus and pancreatic cancer, but researchers cautioned that more studies are necessary to evaluate the nature of the link.

The effective chemoradiotherapy method for pancreatic cancer
Pancreatic cancer is the fifth most common cause of cancer death in Japan. The prognosis is extremely poor because it is difficult to detect this disease in the early stage and also the postoperative incidence of recurrence is still high, and we have not had any effective treatment for inoperable patients.
More Pancreatic Cancer Current Events and Pancreatic Cancer News Articles


Pancreatic Cancer (M.D. Anderson Solid Tumor Oncology Series)

Since the previous M.D. Anderson Solid Tumor Oncology Series publication on pancreatic cancer, there have been major advances in our understanding of molecular events which underlie pancreatic cancer development, both in the sporadic and inherited forms. We have seen the development of the first mouse models that accurately recapitulate features of the human disease. Several landmark clinical...



100 Q&A About Pancreatic Cancer (100 Questions Series)
by Joanne Frankel Kelvin Eileen O'Reilly

EMPOWER YOURSELF! Whether you’re a newly diagnosed pancreatic cancer patient, a survivor, or a friend or relative of someone with pancreatic cancer, this book offers help. The only text to provide a doctor’s and patient’s view, 100 Questions & Answers About Pancreatic Cancer gives you authoritative, practical answers to your questions about treatment options, post-treatment quality of...



Pancreatic Cancer (Recent Results in Cancer Research)

Although pancreatic cancer is one of the most serious forms of cancers, the outlook for patients could be improved. The lack of clinical symptoms of early, surgically removable disease most often limits curative treatment options. The aggressive tumor cell biology, leading to a locally advanced nature of the disease and to early metastases, allows curative resection in only 20% of patients at the...



Pancreatic Cancer Medical Guide
by Qontro Medical Guides

The Pancreatic Cancer Medical Guide is a publication which has been designed to better help readers understand Pancreatic Cancer. This Qontro Medical Guide has been designed with the reader in mind, and is a useful information source for readers at all levels looking to learn more about Pancreatic Cancer. The Pancreatic Cancer Medical Guide is highly recommended for those interested in...

100 Questions & Answers About Pancreatic Cancer, 2nd Edition (100 Questions & Answers about . . .)
by Eileen O'Reilly

Empower yourself!Whether you're a newly diagnosed pancreatic cancer patient, a survivor, or friend or relative of someone with pancreatic cancer, this book offers help. The only text to provide a doctor's and a patient's view, 100 Questions & Answers About Pancreatic Cancer, Second Edition gives you authoritative, practical answers to your questions about treatment options, post-treatment quality...



Pancreatic Cancer: Pathogenesis, Diagnosis, and Treatment

A distinguished panel of world authorities reviews the current state of today's understanding, diagnosis, and treatment of pancreatic cancer. Their cutting-edge reviews discuss both medical and surgical modalities and include numerous insights into the basic molecular processes underlying the disease. Among the key topics covered are the prospects for early diagnosis using molecular techniques,...



My Journey With Pancreatic Cancer
by Calvin E. Rains Sr.

This book is shared to help all understand the cancer affecting the pancreas which is a vital organ in the digestion of food. Pancreatic cancer is one of the most deadly of cancers affecting the human body. Less than 5% of those diagnosed with Pancreatic Cancer survive the first year. This book is intended to help the patient, their families, and friends to understand the dangers and possible...



Pancreatic Cancer
by Daniel D. Von Hoff (Editor)

Praise for the book “An outstanding text covering all aspects of pancreatic cancer, from embryology through genetics and pathology, and including all avenues of treatment. There are 112 internationally recognized authors, the book is marvelously illustrated, and is a must for all scientists and clinicians interested in neoplasms of the pancreas. It is currently the most up-to-date and...



The Official Patient's Sourcebook on Pancreatic Cancer: A Revised and Updated Directory for the Internet Age
by Icon Health Publications

This book has been created for patients who have decided to make education and research an integral part of the treatment process. Although it also gives information useful to doctors, caregivers and other health professionals, it tells patients where and how to look for information covering virtually all topics related to pancreatic cancer (also Cancer pancreas; Pancreatic cancer), from the...



Pancreatic Cancer - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References
by ICON Health Publications

In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading." Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and...

© 2008 BrightSurf.com