Dr. Langenau gives Scott Michael Carter Memorial Lectureship

We are excited to welcome MGH cancer researcher, Dr. David Langenau, 4pm on Tuesday May 6 to present the second annual Scott Michael Carter Memorial Lectureship, “Self-renewal mechanisms in T-cell Leukemia and Rhabdomyosarcoma”.  The Knight Cancer Institute seminar series lecture will be held in the OHSU Main Hospital auditorium, room 8B60.  
  
For more information on the Scott Carter Foundation, and Scott's selfless legacy, click here.  
  
Live stream 4pm PST:  click here. 

Knight Cancer Institute Seminar Series speaker, Dr. Robin Jones (Seattle)

We are pleased to have Dr. Robin Jones, Director of the Bob & Eileen Gilman Family Sarcoma Research Program of the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance, with colleague physician-scientist Dr. Seth Pollack giving the their joint seminar, "Novel Therapeutic Strategies in Sarcoma" on Tuesday January 17 at 4pm in the OHSU Main Hospital 8th Floor Conference Room 8B60.  The public is welcome, and after the seminar a stream of the lecture will be available here.  

Upcoming Lectureship on Canine Osteosarcoma

Dr. Bernard Séguin will present the first annual Scott Carter Memorial Pediatric Cancer Therapeutics Lectureship 4pm on Tuesday May 3 in the Doernbecher Children's Hospital Vey Auditorium (11th floor).  Dr. Bernard Séguin is Associate Professor of Small Animal Surgery & Surgical Oncology at the College of Veterinary Medicine, Oregon State University.  Dr Seguin received his DVM from the Université de Montréal, and thereafter performed residency at Washington State University and Surgical Oncology Fellowship at Colorado State University.  Dr. Seguin’s area of expertise is cancer surgery and his research interests are surgical oncology and osteosarcoma, a primary tumor of bone. He has a strong interest in developing novel limb-sparing surgical techniques, which are aimed at removing the tumor from the limb while preserving its function.  Dr. Seguin will discuss the similarities between treating human and dog patients with osteosarcoma, and a new study designed to offer personalized cancer therapy with novel new drugs that are specifically chosen for each patient based on the biology of their tumor. This work is a collaboration between the OSU School of Veterinary Medicine and the OHSU Pediatric Cancer Biology Program and Knight Cancer Institute.  Dr. Séguin’s seminar presentation is entitled, “Why Treating Man’s Best Friend Benefits Everyone – The Osteosarcoma Story”.

  

This lectureship is presented in the memory of Scott Carter, a young man who inspired his family and community to find better treatment options for children with cancer.  This annual lectureship is supported by the Scott Carter Foundation.   

  

[ update 5/6/2011:  To see the archived talk online, click here . ]

College Student Dedicated to Curing His Own Cancer Speaks at OHSU

Josh Sommer will discuss how individual patients, patient advocacy groups can help expedite research breakthroughs, accelerate their own cures

WHAT:           Josh Sommer will discuss his campaign to find a cure for a rare bone cancer of the head and spine called clival chordoma, and his belief that patients can and should play an active role in bringing about treatments for their own conditions.

Josh was diagnosed with clival chordoma in 2006 while attending Duke University. Determined to find his own cure, Josh volunteered for two years in an oncology lab at Duke University. In 2008 he received a two-year Echoing Green Fellowship for Social Entrepreneurs for his pioneering work in bridging patient advocacy and research.

Today Josh is executive director of the Chordoma Foundation, an organization he and his mom, Simone Sommer, M.D., founded to unite patients, doctors and scientists to accelerate treatments for chordoma, which typically is resistant to chemotherapy and radiation and is prone to multiple recurrences; the average survival after diagnosis is seven years.

“In a few short years, Josh has created a new culture by which patients interact with top researchers and pharmaceutical companies to accelerate research,” said Charles Keller, M.D., leader of Pediatric Cancer Biology Program in the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital, and a member of the OHSU Knight Cancer Institute and the Oregon Stem Cell Center at OHSU. “Josh exemplifies the need for personalized medicine and the Chordoma Foundation has made possible amazing research in the United States and internationally that has resulted in high-profile, high-impact publications in the scientific journal CELL, among others.”

Josh is the inaugural speaker of the Miles Alpern Levin Lectureship, sponsored by the Miles Alpern Levin Initiative for Rhabdomyosarcoma Research and hosted by the OHSU Knight Cancer Institute and the Pediatric Cancer Biology Program at Oregon Health & Science University Doernbecher Children’s Hospital.

WHEN:          Tuesday, April 26, at 4 p.m. The lecture will be streamed live at this website

WHERE:       OHSU Doernbecher Children’s Hospital, 11th floor, Vey Auditorium, 700 S.W. Campus Drive, Portland, OR 97239

DETAILS:     In addition to addressing the important role of patient advocacy he will focus on various issues and special challenges that are associated with cancer detection, diagnostics, prognostics and treatment of rare cancers; strategies to improve screening, scientific collaborations and interactions, and new technologies.




NOW AVAILABLE:  Click here to view the recorded lectureship.  

  

OHSU Doernbecher Scientists Discover New Approach to Overcoming Drug Resistance in a Childhood Cancer With Low Survival Rates

Discoveries in the lab inform national clinical trial under way at OHSU Doernbecher Children’s Hospital

PORTLAND, Ore. — Researchers at Oregon Health & Science University Doernbecher Children’s Hospital have identified a promising new approach to overcoming drug resistance in children with an extremely aggressive childhood muscle cancer known as alveolar rhabdomyosarcoma. Their findings are published online this week in the journal Molecular Cancer Therapeutics and will be featured on the cover of the journal’s print edition next month.

Rhabdomyosarcoma accounts for more than 50 percent of all soft-tissue cancers in children. Even after extensive therapy, the survival rate among alveolar rhabdomyosarcoma patients with advanced disease is less than 20 percent. Dismal outcomes such as these are what keep researchers in the Pediatric Cancer Biology Program at OHSU Doernbecher working around the clock toward a breakthrough.

“Despite our best efforts, outcomes for metastatic alveolar rhabdomyosarcoma have not improved for decades. That’s why our findings are significant. Our clinical partners now have a new method of mitigating resistance to the current treatment for childhood muscle cancer,” said Jinu Abraham, Ph.D., lead author and senior research associate in the Pediatric Cancer Biology Program at OHSU Doernbecher, and a member of the OHSU Knight Cancer Institute.

Previous studies led by Charles Keller, M.D., leader of the Pediatric Cancer Biology Program at OHSU Doernbecher, have shown an important relationship between increased growth factor signaling through the insulin-like growth factor receptor (Igf1r) and decreased survival in children with alveolar rhabdomyosarcoma, a rare form of muscle cancer that typically occurs in the limbs, chest or abdomen of children and adolescents. Growth factor signaling is required for normal development but impairment of this pathway causes abnormal cell growth.

In the current study, Abraham and colleagues tested whether the non-chemotherapy drug NVP-AEW541 could stop Igf1r signaling in a novel mouse model genetically engineered so that alveolar rhabdomyosarcoma tumors begin and expand in the same places they are found in children. Their results showed the non-chemotherapy drug blocked tumor progression in 33 percent of mice with tumors, but most of the mice developed resistance to the drug. 

To uncover the reason for resistance, the researchers conducted additional experiments that showed Igf1r partners with another tumor surface enzyme known as Her2, which fueled the tumor growth despite the growth factor-inhibiting drug.

“Fortunately, when we treated resistant rhabdomyosarcoma cells with a combination of the Igf1r inhibitor and the Her2 inhibitor Lapatinib, there was a significant increase in tumor cell killing compared with either drug alone,” explained Abraham. “Our study has shown that targeting both Igf1r and Her2 may be a very promising approach in preventing resistance to Igf1r-inhibiting drugs in rhabdomyosarcoma.”

“Understanding why some rhabdomyosarcoma tumors are resistant to Igf1r inhibitors is vital to studying these drugs in the clinical setting. This discovery in the lab gives us an option for trying to overcome this resistance and will guide how we combine these new targeted therapies to treat patients with cancer,” said Suman Malempati, M.D., co-author of the current study and principal investigator for the first national clinical trial using an Igf1 receptor inhibitor in combination with chemotherapy for metastatic rhabdomyosarcoma.

The Children’s Oncology Group (COG) trial, now taking place at OHSU Doernbecher Children’s Hospital and several other COG sites, is the first in North America to incorporate a molecularly targeted drug into a clinical trial for childhood muscle cancer.

The National Cancer Institute, Scott Carter Foundation, Alex's Lemonade Stand Foundation and the Hyundai Hope on Wheels Program funded the current study, “Evasion Mechanisms to Igf1r Inhibition in Rhabdomyosarcoma.”

# # #

Particulars

Jinu Abraham, Ph.D., is a senior research associate and scientific manager of the Pediatric Preclinical Testing Initiative at the Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, at OHSU Doernbecher Children’s Hospital; and a member of the OHSU Knight Cancer Institute

Charles Keller, M.D., is the leader of Pediatric Cancer Biology Program in the Papé Family Pediatric Research Institute, and an associate professor of pediatrics (hematology/oncology) at OHSU Doernbecher Children’s Hospital; and a member of the OHSU Knight Cancer Institute and the Oregon Stem Cell Center at OHSU.

Suman Malempati, M.D., is an assistant professor of pediatrics (hematology/oncology) and director of the Oncology Developmental Therapeutics Program at OHSU Doernbecher Children’s Hospital; and a member of the OHSU Knight Cancer Institute

About OHSU Doernbecher Children’s Hospital

OHSU Doernbecher Children's Hospital is a world-class facility that each year cares for tens of thousands of children from Oregon, southwest Washington and around the nation, including national and international referrals for specialty care. Children have access to a full range of pediatric care, not just treatments for serious illness or injury, resulting in more than 165,000 outpatient visits, discharges, surgeries and pediatric transports annually. Nationally recognized physicians ensure that children receive exceptional care, including outstanding cancer treatment, specialized neurology care and highly sophisticated heart surgery in the most patient- and family-centered environment. Pediatric experts from OHSU Doernbecher travel throughout Oregon and southwest Washington to provide specialty care to some 3,000 children at more than 154 outreach clinics in 13 locations.

Contact:         Tamara Hargens-Bradley, 503 494-8231; hargenst@ohsu.edu
Link:  http://www.ohsu.edu/xd/about/news_events/news/2011/03-30-ohsu-doernbecher-scienti.cfm  

[ art credits: Suresh I. Prajapati ]

Knight seminar speaker, Dr. Amy Wagers

We are excited to welcome Dr. Amy Wagers to OHSU for her seminar on, "Tissue Stem Cells in Aging and Malignancy" to be presented 4 pm Tuesday March 7 in the OHSU main hospital 8th floor auditorium.  Amy is an accomplished stem cell biologist  at the Joslin Diabetes Center, Harvard, who bridges both hematopoetic and myogenic progenitor fields, and her work on stem cell niches has important implications for cancer biology.   

Visiting Speaker, Dr. John Ohlfest

We are grateful to visiting speaker, Dr. John Ohlfest, for his presentation at the Knight Cancer Institute seminar series on the topic, "New Strategies to Generating Effective Immune Responses Against Intracranial Tumors."  Dr. Ohlfest's forward-thinking concepts on model systems and immunotherapy approaches were very well received by a wide audience of neuroscientists, neurosurgeons and neurooncologists.  

Knight Seminar Series for Spring 2011

This seminar series is co-sponsored by the Knight Cancer Institute and the Pediatric Cancer Biology Program. 
  

Upcoming Seminar by Dr. Brian Rubin

Brian Rubin, MD, PhD, Associate Professor of Anatomic Pathology and Director of Soft Tissue Pathology at the Cleveland Clinic, Taussig Cancer Institute, will be visiting OHSU on Tuesday, January 18 to give a presentation entitled, “Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumor.” The seminar will take place from 4 to 5 p.m. in OHSU Main Hospital, room 8B60.

Upcoming Talk by Dr. Robert Krauss

Robert Krauss, P.h.D. will be speaking as a PCB invitee for the Knight Cancer Institute Seminar Series on November 30, 2010 in the OHSU Main Hospital 8th Floor Conference Room (8B60).  Dr. Krauss, Professor of Developmental and Regenerative Biology at Mount Sinai School of Medicine, is a developmental biologist with interests in the Sonic Hedgehog pathway.  His work is relevant to cancer as well as neurology and neuroscience. Dr. Krauss will be presenting a seminar titled: “Modeling the Holoprosencephaly Spectrum in the Mouse: Regulation of Sonic Hedgehog Signaling by Co-receptors.”

  

more about Dr. Krauss' research:

 

The Krauss lab is interested in regulation of cell adhesion and signal transduction pathways during development and how such processes may go awry in disease. We have focused much of our effort on a small group of complex and multifunctional receptor-like proteins of the Ig superfamily. Cdo and Boc have Ig and FnIII repeats in their ectodomains and long, divergent cytoplasmic tails. Cdo and Boc function as components of cell surface protein complexes to influence signaling by cadherins, netrins and Sonic hedgehog (Shh). Cdo promotes skeletal myogenesis in vivo and in vitro. Cdo binds in a cis manner (in the plane of the same cell membrane) to the cell-cell adhesion molecule N-cadherin. N-cadherin ligation during myoblast differentiation stimulates binding of Bnip-2/Cdc42 and JLP/p38a/b complexes to the intracellular region of Cdo and thereby links extracellular cell-cell contact to activation of a pathway (p38a/b) that controls a cell-type specific transcriptional program. In addition, Cdo binds in a cis manner to the netrin and RGM receptor, neogenin to influence netrin-mediated signaling during myogenesis.

 

Cdo and Boc also function as both components and targets of the Hedgehog signaling pathway and feedback network. Cdo and Boc bind directly to Sonic hedgehog (Shh) and promote Shh signaling. Mice lacking Cdo or Boc display tissue-specific loss-of-Shh function phenotypes. Cdo-null animals display holoprosencephaly (HPE). HPE is one of the most common human birth defects and is associated with haploinsufficiency for genes encoding Shh pathway components. Clinical expression of HPE is extremely variable, but it is rarely associated with defects in other Shh-dependent structures, such as the limbs. Mice lacking Cdo display HPE with strain-specific severity and without limb defects, modeling human HPE and implicating silent modifier genes as a cause of variability. Boc-null mice are viable, but removal of Boc from Cdo mutant mice worsens the latter’s HPE phenotype. We have used these mice to develop additional models of HPE that include gene-environment interactions and recapitulate the major features of human HPE.