XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
  Breast
  Skin
  Blood
  Prostate
  Liver
  Colon
  Thyroid
  Endometrial
  Brain
  Therapy
  Risk Factors
  Esophageal
  Bladder
  Lung
  Rectal Cancer
  Pancreatic Cancer
  Bone Cancer
  Cervical Cancer
  Testicular Cancer
  Gastric Cancer
  Ovarian Cancer
  Nerve Tissue
  Renal Cell Carcinoma
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Nov 17th, 2006 - 22:35:04

Pancreatic Cancer Channel
subscribe to Pancreatic Cancer newsletter

Latest Research : Cancer : Pancreatic Cancer

   DISCUSS   |   EMAIL   |   PRINT
Disease progression model of pancreatic cancer developed
May 21, 2005, 00:03, Reviewed by: Dr.

"In terms of clinical presentation, metastatic burden, and histological changes in tissue, this model appears to closely mimic the human disease"

 
Building on previous work, researchers at the University of Pennsylvania School of Medicine have developed an animal model of pancreatic cancer that closely mimics disease progression in humans. From this, they hope to develop new treatments for this deadly disease. Advanced pancreatic cancer is among the most lethal of cancers, with a one-year survival rate after chemotherapy of only 17 to 28 percent of patients, according to the National Cancer Institute.

Sunil R. Hingorani, MD, PhD, and David A. Tuveson, MD, PhD, both in the Departments of Medicine and Cancer Biology, and colleagues, engineered mice to express two mutant genes commonly associated with pancreatic cancer: Kras, an oncogene, and p53, a well-studied tumor suppressor. The investigators linked physiological, cellular, and genomic changes due to mutations in Kras and p53 in the mice to changes similar to that observed in pancreatic cancer patients. They report their findings in the May issue of Cancer Cell.

The disease that develops in the Kras and p53 mutant mouse model demonstrates distinct similarities to human pancreatic cancer at multiple levels. "In terms of clinical presentation, metastatic burden, and histological changes in tissue, this model appears to closely mimic the human disease," says Hingorani.

Clinical symptoms in the mutant mice mirrored those displayed in pancreatic cancer patients, such as abdominal swelling and muscle loss. Similarly, the progression of pancreatic cancer metastases paralleled that seen in the human disease. "In this model, pancreatic cancer metastasizes to the liver, lungs, diaphragm, and adrenal glands, all the same places that human pancreatic cancer metastasizes," says Tuveson.

The frequency of metastases to these various organ sites was also highly similar to that seen in humans. In human patients, 60 to 80 percent develop metastases to the liver; and 50 to 60 percent develop metastases to the lungs. In the genetically modified animals, 63 percent displayed liver metastases, and 45 percent displayed lung metastases�further emphasizing the accuracy of this model in mimicking human pancreatic cancer.

To understand the progression of pancreatic cancer, Hingorani and colleagues studied cell lines derived from primary tumor and metastasized cells. From this, the researchers established the occurrence of genomic instability in the mouse model. Genomic instability�continuous formation of mutated chromosomes�leads to widespread genetic changes throughout the affected cells. Genomic instability is seen in many human epithelial cancers, including pancreatic cancer, and is thought to be a driving force in the transition from local tumor growth to metastases of cancers. According to Hingorani, "This model may prove useful to understanding human pancreatic and other epithelial cancers because the key event of genomic instability that has been very difficult to model in the mouse appears to be recapitulated here."

In the pancreatic tumors and metastases from the mouse model, the investigators characterized other molecules implicated in pancreatic cancer. Often, the expression of molecules such as growth factors and their receptors will offer possible targets for treatment. The researchers were surprised to discover a high degree of heterogeneity in expression among these key molecules across the specimens. After ruling out the likelihood that this variability resulted from additional acquired mutations in known key tumor suppressor pathways, Hingorani suggests, "there may actually be unique genetic routes to pancreatic cancer, such that not all pancreatic cancers are equivalent."

The development of the first animal model for pancreatic cancer that fully imitates the progression of the human condition will likely open many new doors in understanding this debilitating disease. "With a model that can generate the full spectrum of disease, from preinvasive to invasive and metastastic lesions, we can begin to tease out the events that are linked to the progression of pancreatic cancer," explains Hingorani. "In trying to understand what events are required to create and support invasive and metastatic disease, we hope to translate our findings into better therapies," states Hingorani.
 

- They report their findings in the May issue of Cancer Cell
 

uphsxnet.uphs.upenn.edu

 
Subscribe to Pancreatic Cancer Newsletter
E-mail Address:

 

The study was funded in part by the National Institutes of Health, the National Cancer Institute, the National Pancreas Foundation, and an AACR-PanCAN Career Development Award. Study co-authors are Lifu Wang, Chelsea Combs, Therese B. Deramaudt, and Anil K. Rustgi from Penn, as well as Asha S. Multani and Sandy Chang, from M.D. Anderson Cancer Center, and Ralph H. Hruban from Johns Hopkins University.

The Abramson Cancer Center of the University of Pennsylvania was established in 1973 as a center of excellence in cancer research, patient care, education and outreach. Today, the Abramson Cancer Center ranks as one of the nation's best in cancer care, according to U.S. News & World Report, and is one of the top five in National Cancer Institute (NCI) funding. It is one of only 39 NCI-designated comprehensive cancer centers in the United States. Home to one of the largest clinical and research programs in the world, the Abramson Cancer Center of the University of Pennsylvania has 275 active cancer researchers and 250 Penn physicians involved in cancer prevention, diagnosis and treatment.

PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is ranked #3 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three owned hospitals [Hospital of the University of Pennsylvania, which is consistently ranked one of the nation's few "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.


Related Pancreatic Cancer News

Vitamin D May Cut Pancreatic Cancer Risk by Nearly Half
Post operative gemcitabine combination therapy improves survival in pancreatic cancer
Treatment of pancreatic carcinoma by adenoviral mediated gene transfer of vasostatin in mice
FDA Approves Tarceva for Advanced Pancreatic Cancer
Xeloda Dramatically Extends Survival Rates in Pancreatic Cancer
Red Meat Associated With Pancreatic Cancer Risk
3D MRI Useful in Detecting Most Lethal Cancers
New onset of hyperglycemic diabetes in adults age 50 or older - signal of underlying pancreatic cancer
Protein responsible for unchecked cell growth found
Disease progression model of pancreatic cancer developed


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us