CURE Childhood Cancer Foundation Awards Multiyear Grant to cc-TDI

We are pleased to announce that the Children's Cancer Therapy Development Institute was selected to receive a multiyear research grant awarded by CURE Childhood Cancer foundation of Atlanta, GA.  The grant will help fund our CUREfast Cancer Registry for Familial and Sporadic Tumors.  We have pioneered an approach to the difficult decision that some families make when choosing to donate tissue that provides resources to the scientific community to bring about new knowledge and potential new drug treatments for changed outcomes.  We are excited to work with CURE Childhood Cancer and honored to be selected as one of their grantees.  
  ​

  

exciting news

How much is a tumor like a wound?  Will tumor cells interact with the body's normal muscle stem cells, co-opting them for advantage to the tumor?  Can IL-4 Receptor antibodies block this process? These are the questions in our NIH R01 grant application that was scored this week in the top 4% of grants for that review cycle (usually, the top 9% of grants are funded).  We're very excited about this grant, and the probable 5 years of funding to pursue these question that we think will benefit patients with rhabdomyosarcoma in a tangible way.  Kudos to Megan, who took strong work by Imran, Tohru and GH to the next level and made this project possible.

 

a tool for innovation

We are grateful to the Alex' Lemonade Stand Foundation for our new instrument, a Form1 3D printer. With this device we can generate custom tissue culture incubation chambers. This project is pioneered by Kirsten and Richard this Summer.  stay tuned!

Northwest Sarcoma Foundation initiative

We are grateful for the $25,000 directed gift from the Northwest Sarcoma Foundation that facilitates Seattle-Portland collaboration in the genetic and functional characterization of adult bone and soft tissue sarcomas.  This is the second year of this program, which supports collaboration between our laboratory and Dr. Robin Jones at the Seattle Cancer Care Alliance.  

SARC Sarcoma Developmental Research Program

We are grateful to the SARC SPORE pilot grants program which has awarded a 2nd year of funding to our collaboration with Dave Langenau's lab at MGH evaluating myodifferentiation therapies for rhabdomyosarcoma.   

Congratulations, Jinu!

Many congratulations to Jinu, whose grant application entitled, "Molecular Reversal of Relapse in Childhood Muscle Cancer" was chosen for funding by the Friends of Doernbecher Foundation!

Our thanks to the Trey Foote Foundation

We are grateful to the family, board and community supporters of the Trey Foote Foundation for the fundraiser and osteosarcoma awareness event last night at the Fort Vancouver Reserve.  This remarkable evening was organized over 9 months by the students of the International Air and Hospitality Academy (special thanks to Tim Kossow).  This event was both seamless and fun, and we can't thank enough the generous attendees to making the night such a success.    
 
for the Doenbecher - Trey Foote Foundation blog, click here.

our thanks to the Kyla McCullough GIft Fund!

We are grateful to the Kyla McCullough Gift Fund who today presented a check for the purchase of a
multiwell electroporator instrument.  This instrument allows our researchers to perform highly efficient genetic studies of primary tumor cells and cell lines -- a completely new set of experiments we could only do with this special instrument!  It was great to spend time today with Bret, Brettie, Jen and Matt.  Kyla has a daily presence in our research. 

Childhood cancer foundations partner towards a clinical trial with OHSU-Doernbecher

press release adapted from The Doernbecher Connection (Winter 2014, Issue 3) 

Beech Grove, KY;  Miami, Florida; Portland, OR

Two children who found worldwide acclaim through their inspirational battles with childhood cancer continue to make an impact. The Thumbs Up for Lane Goodwin Childhood Cancer Foundation and the Live Like Bella™ Foundation for Childhood Cancer have announced the joint funding of the $180,000 “Lane-Bella Project.” The Lane-Bella Project, under the direction of Charles Keller, M.D., an associate professor of pediatrics at Oregon Health and Science University Doernbecher Children’s Hospital and a member of the OHSU Knight Cancer Institute, is a new set of studies to prepare for a clinical trial focusing on Rhabdomyosarcoma, the aggressive childhood cancer that took the lives of both Lane Goodwin, age 13, and Bella Rodriguez-­‐Torres, age 10. The study will focus on finding an antibody to stop the growth of childhood muscle cancers. Once preclinical studies are complete, children around the world might benefit from these new innovations as early as 2015. The trial is the largest project funded by the two foundations, with each contributing $90,000, and includes the $20,000 donation that the MLB National League Rookie of the Year, Marlins Pitcher Jose Fernandez, directed to the Live Like Bella™ after receiving the honor.

“I want to help children with cancer. I’m proud to support life changing research to help find a cure.”   ‐Jose Fernandez 

Gifts designated for the Lane-­Bella Project will also be applied to the historic Knight Cancer Challenge. Nike co-founder Phil Knight and his wife, Penny, will match OHSU’s fundraising efforts if it meets its $500 million fundraising goal by the end of 2015, totaling $1 billion to advance the Knight Cancer Institute’s vision to end cancer as we know it. To learn more, visit ohsu.edu/knightcancerchallenge.

The Thumbs Up for Lane Goodwin Childhood Cancer Foundation works in memory of its founder, Lane Goodwin. It funds cuttng edge research to find a cause and a cure for childhood cancers, empowers families to advocate on behalf of their children, and provides financial assistance to families through the “Changing Lanes” program. For more information, visit www.ThumbsUpForLane.org

The Live Like Bella™ Foundation was founded in memory of Bella Rodriguez-­‐Torres. It funds innovatve pediatric cancer research, provides recreatonal support for families with children in treatment and assists families who have lost a child to cancer.
For more informaton, visit
www.LiveLikeBella.org.
#ThumbsUpForLane
#LiveLikeBella
#LaneBellaProject
#NoChildFightsAlone

ALSF REACH grant highlighted in Portland Business Journal

Megan's project, sponsored by the Alex's Lemonade Stand Foundation, was highlighted today by Elizabeth Hayes in the Portland Business Journal.  For project updates, click here.  

International group of pediatric brain cancer researchers receives $300K toward a cure

press release

Parents of children who died from rare cancer believe greater investment in quality research is critical

PORTLAND, Ore. – An international consortium of researchers focused on identifying new molecularly targeted drugs to treat the most fatal form of childhood brain tumor, diffuse intrinsic pontine glioma, or DIPG, has been awarded nearly $300,000 by The Lyla Nsouli Foundation for Children's Brain Cancer Research, based in London, England. The foundation was established in memory of 3-year-old Lyla Nsouli, who died in January 2012 after a devastating five-month battle with DIPG.

Lyla’s parents, Nadim and Simone Nsouli, are hopeful their contribution will help bring researchers closer to a cure: “Facing her sudden, brutal diagnosis without any real option for treatment or survival is not an experience any child or their family should ever have to bear. Significantly greater investment in quality research is vital to improving the prognosis for children like Lyla. We are determined that research can provide treatments and eventually a cure for this cruel childhood cancer.”

To date, no treatment does more than incrementally increase survival of children with DIPG. One day a child may have a headache or unsteadiness, but the next day a family's life and plans are tragically changed. A group of international researchers called the DIPG Preclinical Consortium hopes to change this.

“Our first phase of drug screening and tumor DNA sequencing couldn't have been possible without the support of the Lyla Nsouli Foundation, the Cure Starts Now, Accelerate Brain Cancer Cures and CureSearch Foundations. Now that we have drug leads, the hard work of validating these begins. The Lyla Nsouli Foundation has been with us every step of the way, both in terms of support and accountability — both matter,” said consortium coordinator Charles Keller, M.D., associate professor of pediatrics at Oregon Health & Science University Doernbecher Children’s Hospital and the OHSU Knight Cancer Institute.

“The members of the Children’s Oncology Group CNS committee express a deep sense of gratitude to the Lyla Nsouli Foundation for funding the DIPG Preclinical Consortium,” said Amar Gajjar, M.D., chair of the brain tumor committee for the National Cancer Institute-supported Children's Oncology Group (COG). “The grant from the foundation has sparked a global effort to find new and effective therapies using the latest technologies currently available against diffuse intrinsic pontine glioma. The rapid translation of information from research laboratories to a clinical protocol is an often sought aim for advancing cancer cure rates – the grant from the Lyla Nsouli Foundation has made this dream a reality.”

Gajjar and Maryam Fouladi, M.D., co-chair of the COG brain tumor new agents committee and leader of its Pediatric Brain Tumor Consortium, conceived the DIPG Preclinical Consortium with Keller: “Real-time science in partnership with the community for a shared goal of finding a two-drug combination to put into international clinical trials for DIPG.”

Consortium member Jacques Grill, M.D., Ph.D., Institut Gustave-Roussy, Villejuif, France, innovates by creating living cell cultures not from autopsy-derived tumor samples, but from biopsies from the brainstem. This novel approach was initially controversial but is winning acceptance, Keller noted. 

“Grill and his colleague, Dr. Darren Hargrave at Great Ormond Street Hospital, London, keep a clear line of communication so that the consortium's results are reported in real time to the European clinical trial groups to inform on that side of the Atlantic,” said Keller. “The scientific teams are diverse due to the pressing nature of the need to understand and treat DIPG.”

Each member will take a different but complementary role to ensure the results of the robotic drug screen of 17 autopsy- or biopsy-derived DIPG cultures can be validated in mouse models.

"This collaboration has been a wonderful opportunity to work together as a community to move the field closer to an effective therapy for this terrible disease. I am hopeful that, together and with the immense support from Lyla Nsouli Foundation, we will make real strides forward now," said Michelle Monje, M.D., Ph.D., Stanford University Beirne Faculty Scholar in Pediatric Neuro-Oncology, Stanford Cancer Institute, Lucile Packard Children's Hospital.

"The DIPG Preclinical Consortium offers hope where once there was very little. When my son, Andrew, was diagnosed with DIPG in October 2007, I never imagined that such a collaboration would exist a few short years later — a collaboration where exceptional science and a remarkable patient community meet in partnership to change the future for children like Andrew and Lyla," said DIPG parent Sandy Smith.  

# # #

Consortium members include: Keller, Kellie Nazemi, M.D., Nathan Selden, M.D., Ph.D., Doernbecher Children’s Hospital, Oregon Health & Science University; Monje, Stanford University; Grill, Institut Gustave-Roussy; Oren Becher, M.D., Duke University Medical Center; Cynthia Hawkins, M.D., Ph.D., University of Toronto; Xiao-Nan Li, M.D., Ph.D., Baylor College of Medicine; Esther Hulleman, VU Cancer Center Amsterdam; Eric H. Raabe, Johns Hopkins University; Katherine Warren, Paul Meltzer and Martha Quezado, NIH; and Marta Alonso, University of Navarra, Madrid, Spain.  

The DIPG Preclinical Consortium is funded by the Lyla Nsouli Foundation for Children’s Brain Cancer Research, the Cure Starts Now, Accelerate Brain Cancer Cures and CureSearch Foundation.

ABOUT OHSU DOERNBECHER CHILDREN’S HOSPITAL

OHSU Doernbecher Children's Hospital ranks among the nation’s "Best Children’s Hospitals."* It is one of only 22 National Institutes of Health-designated Child Health Research Centers in the country and ranks 39th for NIH awards to children's hospitals and their university-affiliated department of pediatrics.**

Nationally recognized physicians and nurses at OHSU Doernbecher provide a full range of pediatric care to tens of thousands of children each year from Oregon, Southwest Washington and around the nation in a family-centered environment. OHSU Doernbecher specialists also travel throughout Oregon and Southwest Washington, caring for more than 3,000 children at more than 200 outreach clinics in 15 locations. Neonatal and pediatric critical care experts provide round-the-clock consultations to community hospitals statewide through OHSU Doernbecher's state-of-the-art telemedicine network.

*U.S. News & World Report 2013-14 Best Children’s Hospitals

** National Association of Children’s Hospitals and Related Institutions (NACHRI)

ALSF REACH Grant!

We are grateful to the Alex's Lemonade Stand Foundation for funding to enable the translation of a basic science discovery to preclinical trials so that Children's Oncology Group phase I and II trials might be possible.  The discovery of EphB4 as a therapeutic target in alveolar rhabdomyosarcoma was work of former HHMI medical student fellow, Imran Aslam (now a JHMI internal medicine resident).  Working in collaboration with the Druker laboratory, Imran uncovered the EphB4-EphrinB2 as the potentially highest value target in rhabdomyosarcomas.  This ALSF REACH award allows us to investigate an anti-EphB4 antibody in embryonal rhabdomyosarcoma, as well as an EphB4-nanoparticle sump in alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma and osteosarcoma.  This work will be carried on by our star muscle- and mouse models expert, Megan.  Check back regularly for updates on Megan's progress!

project updates:

01/14/2014:  Project Funded!
  
02/06/2014:  The immunocompromised mice we will be using to test the efficacy of an anti-EphB4 antibody have arrived. These mice will be used to create pilot orthotopic xenograft models of eRMS in the coming weeks.  
[ picture:  at center is Megan. ]  
  
02/20/2014:  This week, the first set of immunocompromised mice were injected with Rh18 cells (a human derived eRMS cell line). This begins a pilot study to demonstrate the latency with which a xenograft from this cell line will successfully create tumors in the strain of mice that we will use for future Alex’s Lemonade Stand experiments. In other strains of immunocompromised mice, Rh18 cells have generated tumors in 6-8 weeks- we’ll have to wait and see if these mice follow suit!
  
02/27/2014:  Currently we are growing a new cell line to inject into the mice which are part of our pilot experiment. To be consistent between experiments, we need the same amount of cells for each mouse we use. This new cell line is a little slow growing; as it is with many other research experiments, the hardest part is waiting!
  
03/14/2014:  more watchful waiting (nothing new).
  
03/20/2014:  A second round of cells have been injected into immunocompromised mice this week to continue our pilot experiments for this Alex’s Lemonade Stand project. Our next steps will be to observe these mice over the next few weeks and take note of when the tumor cells engraft and begin to grow.
  
03/27/2014:  no new news.  still in watchful waiting mode. 
  
04/04/2014:  still awaiting tumor development before initiating drug trials. 
  
04/10/2014:  Our pilot study is progressing nicely this week, with 3 of our orthotopic xenograft mice developing tumors. We will continue to observe our other injected mice for tumor development over the next several weeks.
  
04/14/2014:  See the blog post  http://kellerlabblog.blogspot.com/2014/04/imrans-paper-published-in-pnas.html for a link to today's published PNAS paper on this topic.  The studies in Imran's paper were the basis of this "next steps" project.  
  
04/17/2014:  The growth of the current tumors is progressing as expected. Our second group of mice have not grown any tumors yet, but they are still within the expected latency time for development. We continue to monitor them daily.

04/24/2014:  New batch of EphinB2-neutralizing biological agent received from pharma partner, facilitating the next series of therapeutic studies. 
  
05/08/2014:  mouse studies about to start for EphinB2-neutralizing biological agent. 
  
05/15/2014:  This week our official investigation on the efficacy of an EphrinB2-neutralizing agent has begun. The study mice arrived on Wednesday and were injected with Rh18 cells, a well characterized human eRMS cell line. Using our pilot data, we expect tumors to form within the next 2-3 months. Additionally, our second pilot study is still ongoing; we are continually monitoring the mice for development of tumors.
  
05/21/2014:  Rh18 xenograft studies still ongoing. 
  
05/28/2014:  not unexpectedly, still waiting on tumors to develop before treatments can begin...
  
06/05/14:  No new news to report this week. We do not expect treatment on our experimental mice to begin for a few more weeks, and we are continually monitoring both our initial pilot mice and current experimental for tumor development.
  
06/12/2014:  Still patiently waiting this week for mice in both experimental groups to develop tumors.  

06/26/2014:  Tissue microarrays of EphB4 and EphrinB2 on embryonal rhabdomyosarcoma are complete (it will take 1-2 weeks to analyze these with our pathologist collaborator).  We are also still patiently monitoring our immunocompromised mice for development of tumors. We are checking them 3 times a week so as soon as tumors develop we can begin treatment. Stay tuned!

  
07/10/2014:  Exciting news from the Keller Lab for our Alex’s Lemonade Stand project this week! The immunocompromised mice have started growing small tumors for the Rh18 eRMS cell line. In the coming weeks, most will begin receiving either an EphrinB2-neutralizing agent or a control drug.  Each mouse will be monitored daily and tumors measured three times per week.  This experiment is progressing on schedule and the next few months should be full of interesting data.

  
07/18/2014:  The Alex’s Lemonade Stand experiment is progressing nicely this week. All mice are tolerating the dosage of the drug well, and are not exhibiting any side effects/toxicity.  Expression of EphB4 and EphrinB2 in a small set of human osteosarcoma samples verified (request for TMA sent to COG); early studies of neuroblastoma are promising.  
  
07/31/2014:  This week, our experimental mice continue to be monitored daily. We will be wrapping up the in vivo testing in the coming weeks, then moving on to the data analysis phase.
  
08/08/2014:  EphB4 and EphrinB2 immunohistochemistry optimized for canine osteosarcoma (for pets with spontaneous osteosarcoma a potential preclinical model to help the dogs, and plan for a human osteosarcoma trial.)  Request sent to NCI comparative oncology program for canine TMA slides.  Meanwhile, the Rh18 eRMS mouse studies with the EphrinB2-neutralizing agent are wrapping up. 

  
08/21/2014:  The in vivo portion of our Alex's Lemonade Stand project is slowly coming to a close. This week some of the raw data analysis and number crunching was started, although it will be several weeks until that is finished. Additionally, there are various supporting experiments that still need to be executed to fully determine the efficacy of the EphrinB2 blocking agent. 
  
09/11/2014:  This week our supplemental experiments continue. We are now using RT-PCR to examine the amount of metastasis in the harvested lungs of our treated and control mice. These experiments are time consuming, but will help us decide if the EphrinB2 neutralizing agent administered to the mice was effective in diminishing the metastatic capability of RH18 cells.  

10/02/2014:  Canine osteosarcoma TMA's for staining received; COG neuroblastoma TMA slides approved but MTA still to perform; COG osteosarcoma TMA proposal still in review (since July). rt-pcr strategy for above EphrinB2 blocking agent mouse studies (completed) is in revision.  Some delays occurred as Megan spent the last 3 weeks in a collaborator's lab at Cold Spring Harbor Laboratory for a new strategic collaboration.    
  
10/16/2014:  A few setbacks this week owing to the particularly specific requirements of some molecular biology techniques. We have ordered a few new reagents in an attempt to complete the RT-PCR experiments, and should be back at the bench soon.
  
10/30/2014:  Our new reagents for the revised experiments have just arrived, and soon we should have a clear picture about the efficacy of the EphrinB2 blocking agent on lung metastasis.
  
12/04/2014:  Preclinical trial of sEphB4-HSA in Rh18 orthotopic xenografts is now complete.  The next step is preclinical testing in a patient-derived xenograft (see the description of this autopsy-derived model).  

  
12/31/2014:  Project on short term hold pending transfer of grant from OHSU to our new, bold adventure at cc-TDI. 
  
01/06/2014:  New lab at cc-TDI started!
  
01/07/2014:  Collaborators Ayeza Bajwa and Atiya Mansoor have completed analysis of human eRMS tissue microarrays with unexpected results that point to key differences in aRMS and eRMS with respect to EphB4 and EphrinB2 biology. 
  
01/08/2015:  ALSF REACH grant year 2 funding received... this is the first grant funding for cc-TDI ... thank you, ALSF!
  
01/15/2015:  Strategic meeting (teleconference) held including pharma and CSU partners to consider a companion animal trial for osteosarcoma using EphB4/EphrinB2 therapeutics.  
  
01/27/2015:  Integration of animal study underway by Matthew, including ongoing tissue analysis from these studies.  
  
02/06/2015:  We have begun considering approaches to separating cell-autonomous and tumor microenvironment contributions of EphB4-EphrinB2 signaling in eRMS.  

02/13/2015:  analysis of tumor cell vs stroma cell expression of EphB4 and EphrinB2 reveals distinct differences in alveolar and embryonal rhabdomyosarcomas.

02/20/2015:   For Rh18 xenograft studies (completed), lung metastasis counts are in progress and pharmacodynamic studies are planned.
  
02/27/2015:  COG TMA requests for osteosarcoma and neuroblastoma slides are approved, but MTAs are still in progress. 
  
03/04/2015:  Rh18 xenograft pharmacodynamics studies in progress.
  
05/06/2015:  Rh18 xenograft pharmacodynamics studies done; Rh18 lung metastasis count in progress. 
  
05/20/2015:   COG osteosarcoma TMA slides arrived May 8; working to verify EphrinB2 expression in PDX models.
  
06/03/2015:  Rh18 xenograft lung metastasis count done.
  
07/29/2015:  CTEP approved neuroblastoma TMA slides protocol July 26.
  
08/07/2015:  westerns on PDXs still ongoing; neuroblastoma TMA slides received.

The Lane-Bella Project

We are grateful to the Live Like Bella Foundation and the Thumbs Up for Lane Goodwin Childhood Cancer Foundation for co-funding our Lane-Bella Project, "towards a clinical trial of the VasG3 antibody in alveolar rhabdomyosarcoma".  This work is not only supported by a very generous gift from National League Rookie of the Year, Jose Fernandez, but also by families that have been touched by rhabdomyosarcoma.  Angie and Shannah will hold us accountable, and so check back frequently for project updates from Jinu & Charles in this blog entry!

weekly blog update:
12/31/2013:  funding arrived!  we are also filmed a short video to explain the project, to be available soon!
  
01/01/2014:  the video...
  

01/09/2014:  while we wait for the internal university process for account setup, we have begun conversations with the pharma on antibody doses to use for initial studies.
  
01/17/2014:  irb and iacuc approvals are in place so that the university account can be set up.
  
01/24/2014:  accounts set up.
  
01/30/2014:  requests for antibody sent to pharma partner.  mice for studies ordered.
  
02/06/2014:  mice for initial/pilot studies received.  cells thawed for expansion - needed before implantation into mice.  first experiment's plan reviewed with team.
  
02/13/2014:  We have three human aRMS cell lines in culture for injection into immune-deficient mice. Rh41 is growing well and will be injected into mice early next week. Rh5 and PCB380 are taking time to recover from cryopreservation.  See also the press release. 
  
02/20/2014:  Rh41 tumor cell innoculations done today.  
  
02/27/2014:  No new news.  We are waiting for the Rh41 injected mice to grow tumors. 
  
03/06/2014:  As expected, still watchful waiting on Rh41 mice. 
  
03/14/2014:  Discussed studies with pharma company.  more watchful waiting of Rh41 mice. Rh5 mouse studies initiated this week. 
  
04/03/14:  Rh41 xenografts beginning bear palpable masses.  
  
04/10/2014:  Rh41 latency confirmed; Rh5 latency studies still underway; stay tuned for a related publication announcement on Monday!

  
04/14/2014:  See the blog post  http://kellerlabblog.blogspot.com/2014/04/imrans-paper-published-in-pnas.html for a link to today's published PNAS paper on this topic.  The studies in Imran's paper were the basis of this "next steps" project.  
  
04/17/2014:  Rh41 tumor growth rates in NSG mice has been determined & experiment ended.  Rh5 beginning to form tumors. 
  
04/24/2014:  Rh5 xenografts progressing as expected.  New batch of EphB4 neutralizing antibody received from pharma partner, facilitating the next series of therapeutic studies. 
  
05/01/2014:  Rh5 pilot tumor growth rate studies complete.  Therapeutic studies to follow. 
  
05/08/2014:  Working with partner (Jax) to plan PCB380 (aRMS) patient-derived xenograft testing with the EphB4 neutralizing antibody.
  
05/08/2014:  partnership experiment continues to be in preparation phase. 
  
05/15/2014:  no specific progress this week (still awaiting partner preparations). 
  
05/21/2014:  PCB00380 studies may begin in 1-2 weeks.  Meanwhile, discussions with COG leaders this week indicate that phase I testing will be made much easier if we can demonstrate EphB4 blocking antibody activity in 2 or more additional pediatric cancers.  This is fair.  In an a related project, we have been examining osteosarcoma (very early studies) and neuroblastoma is a possible other cancer to consider. 

05/29/2014:  no new news to report. 

06/06/2014:  We are happy to welcome our Summer student Renae to the lab.  Renae will be assisting Jinu in our EphB4 RMS studies.  Meanwhile, PCB00380 experiments are about to commence.  It will take ~6 weeks for these tumors to arise, and will reach the size for treatment to begin in 12-16 weeks.  
  
06/12/2014:  still awaiting tumor formation. interestingly, our Summer student Teagan has found both EphB4 and EphrinB2 expression in canine osteosarcoma.  There are a lot of other studies to consider, but companion pet cancer patients often can be the first to receive a treatment on its way to pediatric cancer trials.  more to follow on this very early observation. 
  
06/26/2014:  parallel studies are now ongoing to explore human osteosarcoma expression of EphB4 and EphrinB2.  We're still awaiting tumor growth of the alveolar rhabdomyosarcoma mice.   
  
07/18/2014:  still awaiting tumor growth.
  
07/26/2014:  still no growth of tumors implanted in June.  Considering parallel model intiation.
  
08/08/2014:  patient-derived human xenograft (PDX) models are slow to grow!  We will start xenograft studies using human aRMS cell lines in the coming weeks: results from the PDX and orthotopic cell line xenografts should both be completed by November/December.  
  
09/11/2014:  awaiting tumor growth.  have been invited to present the data thus far to a cooperative sarcoma clinical trials group on October 7 in Gaithersburg. Parallel studies of EphB4 as a therapeutic target in osteosarcoma continue to look promising.  
  
10/02/2014:   we received as second batch of VasG3 antibody from the company, and have ordered a new set of mice for the Rh30 cell line xenograft studies.  Still awaiting PDX tumor growth.  
  
10/16/2014:  new set of mice due in 2 weeks.  Meanwhile, Jinu is gearing up to have enough cells (for this and another study).  That's a lot of plates!
  
10/30/2014:  All 25 mice have received Rh30 aRMS cells. We are waiting for the tumors to develop in these mice to start treatment with EphB4-antibody from Vasgene.
  
11/13/2014:  For the Rh30 aRMS cell line studies, tumors in mice are palpable and the mice are being treated with the EphB4 antibody.  For the PCB00380 patient-derived xenograft studies, we implanted 5 mice in June and another 5 in August.  We are seeing tumor growth in the August batch.  Both tumors are quite small.  We might see the tumors reach a modest size in late December at which time we can split the tumor in order to generate the many-needed study mice.  This model is slow, so EphB4 antibody dosing will probably begin in March and wrap up in May 2015.  This is the nature of a more authentic patient-derived xenograft (PCB00380) versus the cell line xenografts with Rh30 (Rh30 was created way back in 1987... it's hard to say whether all of its biology is representative of the disease in 2014; however, for the field Rh30 is (unfortunately) still a standard model).   

 

12/11/2014:  Preclinical trial of Rh30 xenograft animals treated with VasG3 is now complete and under analysis. 

 

12/31/2014:  Project on short term hold pending transfer of grant from OHSU to our new, bold adventure at cc-TDI. 

01/06/2015:  New lab started!

  
02/04/2015:  Still awaiting transfer of grant.  Meanwhile for he PCB00380 patient-derived xenograft studies (aRMS model), tumors implanted in December are still too too small to begin treatment.   

02/13/2015:  Thank you, LiveLikeBella, for the funds to initiate the first half year's project!  PCB00380 tumors large enough to begin treatment with VasG3. 

02/18/2015:  PCB00380 treatment studies ongoing.

02/27/2015:  PCB00380 treatment studies still ongoing.
  
03/12/2015:  For PCB00380 treatment studies, synchronous enrollment was done (treatment started on the same day for all tumors).  Some tumors were smaller than others, and it appears that they were at different growth rates.  To have more consistent data, we are going to repeat the experiment with asynchronous enrollment... that is, tumors of the same size begin treatment, even if different tumors begin treatment on different days.
  
03/25/2015:  Repeat study of PCB00380 started (tumors innoculated). 
  
04/08/2015:  New supply of VasG3 received from the manufacturer; ready for repeat mouse study.  
  
04/20/2015:  Awaiting tumor growth in PCB00380 animals.
  

05/07/2015:  In keeping with our publication this past year (PDGFRβ reverses EphB4 signaling in alveolar rhabdomyosarcoma, Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6383), we are next going to test the combination of VasG3 (to inhibit EphB4) and imatinib (to inhibit PDGFRb).  A video progress report is below:  

05/07/2015:  repeat of VasG3 inPCB00380 is underway.  
  
06/03/2015:  pharmacodynamics of VasG3-treated Rh30 xenografts in progress.
  
06/17/2015:  no growth so far for repeat of VasG3 inPCB00380.


06/03/2015:  pharmacodynamics of VasG3-treated Rh30 xenografts is done.
  
07/15/2015:  lung metastasis count of VasG3-treated Rh30 xenografts in progress.
  
07/28/2015:  repeat of VasG3 inPCB00380 is nearly complete.  lung metastasis count of VasG3-treated Rh30 xenografts is done. 
  
08/05/2015:  checking PDXs for best model to try VasG3 - other agent combinations. 
  

Patrick M. Callahan Memorial Fund

We are grateful to the Patrick M. Callahan Memorial Fund for their generous 2013 gift, which makes possible pilot studies of new research for the childhood muscle cancer, rhabdomyosarcoma.  The community of supporters of the Patrick M. Callahan Memorial Fund, and Patrick's mother Joann, are valued partners in the mission to make rhabdomyosarcoma a uniformly survivable condition.  

Congratulations, Mat!

Lab member Mathew Geltzeiler has selected to receive this year’s American Academy of Otolaryngology – Head & Neck Surgery Foundation (AAO-HNSF) Saidee Keller Memorial Resident Research Grant.  We couldn't be more proud of Mat's accomplishment! 

Postdoctoral Position Available!

This mentored position will empower the candidate to analyze complex conditional genetic mouse models of pediatric cancers for the purpose of developing novel molecular therapies. The primary goal for this fellowship is to understand the role of growth factors & kinases in the progression of the childhood muscle cancer, rhabdomyosarcoma. Employing molecular biology, biochemistry and multiscale imaging (whole animal to confocal microscopy), the candidate will have the opportunity to identify critical factors in tumor maintenance and tumor progression from which new therapies can be developed.  Rapid translation to the clinic is the underlying goal.  Candidates with experience in developmental biology or muscle biology are especially encouraged to apply.  
  
Applicants will be able to find the position by entering IRC39103 into the search field on www.ohsujobs.com.  For question, you can contact Charles via email, keller (at) ohsu.edu.  
  
[ photo credit, Mat Geltzeiler ]

Our thanks to the Kyla McCullough Gift Fund

We are grateful to the community of supporters for the Kyla McCullough Gift Fund who have made possible the purchase of a high-throughput multi-well plate reader for our program's study of childhood cancer. This instrument will be used multiple times a day, and enables us to perform research at a new and much faster pace.  

NWSF funds UW-OHSU Sarcoma Studies

We are grateful for the $25,000 directed gift from the Northwest Sarcoma Foundation to facilitate the collaborations with our University of Washington colleagues, including Dr. Robin Jones.  These funds strengthen the bonds between our two institutions and (hopefully) does a great deal to advance knowledge, and eventually care, of sarcoma patients in the Pacific Northwest and beyond. 

Rally Foundation Milestone

Congratulations to the Rally Foundation for reaching the $1M milestone for grant funding in 2013.  We are also grateful for the support of Rally Foundation in our lab's projects, currently and over many years.  

NCI funds sarcoma study

We are excited to be part of the program project NF-kB Regulated Metabolic Shifts in Childhood Sarcomas directed by Dr. Peter Houghton at Nationwide Children's Hospital and newly funded by NIH/NCI.  The studies within the project led by Dr. Denis Guttridge in which we will participate will investigate the NFkB signaling pathway in rhabdomyosarcoma.