New Tools in Pancreatic Cancer Research

Understanding Xenograft Rejection

Deep Brain Stimulation Effect Indirect

Update

Upcoming Centre
for UHN Trainees

Canada cancer study shows age a factor in treatment decisions


The older a cancer patient, the less likely they will receive treatment or enroll in a clinical trial, according to a recent study led by UHN's Dr. Lillian Siu (OCI/PMH), Dr. Sharon Straus (TGRI/TGH) and clinical fellow Dr. Carol Townsley (OCI/PMH). Using data from the Ontario Cancer Registry and by extensive chart review of patients treated at PMH and Northwestern Ontario Regional Cancer Centre, the team evaluated whether age, independent of other factors, can predict whether a person will receive cancer treatment services in Ontario.

Says Dr. Siu, “This finding is only the first step in improving cancer services for elderly patients. It reveals the need to educate oncologists about how to care for elderly patients and to increase enrolment of elderly patients into clinical trials to better understand the effects of drugs in this age group. These tactics may aid health professionals to better understand which therapies are best suited for treating elderly patients. Age alone should not be the barrier to provide older patients standard therapies or to enroll them into appropriate clinical trials.”

J Clin Oncology 2005 Jun 1;23(16):3802-10. [PubMed abstract]

Institutes: OCI/PMH
Division: Clinical Studies Resource Centre


Engineered cells used to reveal potential pancreatic cancer markers



New tools from the lab of Dr. Ming Tsao will be used to identify markers for early detection of pancreatic cancer—a cancer called the “silent killer” since it offers few symptoms and is often diagnosed when it is well advanced. The tools are two sets of genetically engineered cells that model two stages of pancreatic cancer: the early pre-cancerous lesions in the pancreas and the later stages of pancreatic cancer. A gene, LAMB3, was identified as showing increased expression during cancer progression.

“Our cell lines have provided a mechanism for evaluating gene expression changes during pancreatic cancer development. Using them, we've shown that monitoring LAMB3 may thus be a way of detecting pancreatic cancer earlier, in the absence of physical symptoms of the cancer. Further studies on this potential biomarker are ongoing," says Dr. Tsao.

Cancer Res. 2005 Jun 15;65(12):5045-53.[PubMed abstract]
Research supported by the Canadian Institutes of Health Research, US Public Health Services and the Lockton Fund for Pancreatic Cancer Research.

Institute: OCI/PMH
Division: Applied Molecular Oncology

Xenograft transplantation: handling rejection


UHN researchers Drs. Thomas Waddell and Myron Cybulsky (TGRI/TGH) have shed new light on a major obstacle to xenograft transplantation—a potential alternative to the organ transplants desperately needed by more than 3,900 Canadians [Canadian Institute for Health Information, 2004].



Xenografts—organs transplanted from one species to another—are rejected by the human immune system. In xenograft rejection, immune cells called monocytes accumulate and attack the foreign organ. In experiments with monocytes from humans and heart cells from pigs, the UHN team showed that the attachment of human monocytes was mediated by a molecule called alpha-Gal on the surface of the pig cells.

Dr. Waddell says, “These results help us to understand the molecular mechanisms behind xenograft rejection. By examining how monocytes are activated we can develop strategies for preventing the rejection.”

J. Immunol. 2005 Jun 15;174(12):8072-81.[PubMed abstract]
Funded by the Canadian Institutes of Health Research and the Cystic Fibrosis Foundation.

Institute: TGRI/TGH
Division: Cellular & Molecular Biology

Digging deep in brain stimulation


Drs. Robert Chen, Andres Lozano, Anthony Lang, and Elena Moro (TWRI/TWH) and PhD student Greg Molnar have provided strong evidence that deep brain stimulation (DBS)—an effective treatment where a device is surgically implanted in the brain to deliver electrical impulses—controls tremors by stimulating neurons rather than inhibiting them.



The mechanism behind deep brain stimulation (DBS) of the thalamus—the part of the brain responsible for processing motor and sensory information and sending it to other parts of the brain—has remained elusive. Initially it was thought that DBS worked by directly inhibiting the neurons it was acting on, but recent studies have suggested otherwise.

“We compared brain activity in patients receiving DBS to brain activity in healthy individuals receiving magnetic brain stimulation—a painless way to stimulate the brain. Our results show DBS actually activates neurons that then interfere with the transmission of the faulty signals that cause tremors,” says Dr. Chen.

Knowledge of the pathways involved in DBS will ultimately help develop better medical and surgical therapies for the diseases it’s used to treat.

Neurology. 2005 Jun 14;64(11):1913-9 [PubMed abstract]
Research supported by the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Ontario Innovation Trust, and Meditronic Inc.

Institute: TWRI/TWH
Division: Applied & Interventional Research

New centre for UHN trainees to be launched


The Centre for Research EDucatIon & Training (CREDIT), to be launched in the fall, will examine current practices in research training at UHN and seek to develop improved policies and processes for many issues relating to the research training experience.

Three outstanding research educators have stepped forward to be the site directors for CREDIT: Frances Skinner at TWRI; Mingyao Liu at TGRI, and David Rose at OCI. The overall program director will be David Rose.

“Students and post-doctoral fellows are critical members of the UHN research community making this an important initiative,” says Dr. Christopher Paige, VP Research.