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Children’s, Pitt Researchers Explain Cancer Gene Role in Growth of Pediatric Liver Tumors

PrintResearchers at the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC have uncovered how a key cancer gene works to accelerate cell growth in a mouse model of pediatric liver tumors. The results provide a better understanding of how inhibition of this gene can be used to combat the disease, and also suggest that doing so may be associated with fewer side effects than originally assumed. The findings were published in the Journal of Biological Chemistry, and selected as one of the journal’s “Papers of the Week.”

The new research focuses on one of cancer’s key genetic players, a gene called Myc.

“Understanding how Myc leads to tumor growth can provide valuable insight we can use to treat the disease, since at least 50 percent of all cancers overexpress Myc in some way,” explained lead study investigator Edward Prochownik, MD, PhD, director of oncology research, Children’s Hospital, and the Paul C. Gaffney Professor of Microbiology and Molecular Genetics at Pitt’s School of Medicine.

Dr. Prochownik’s research concentrates on the role of Myc in liver tumors. His team previously showed that although Myc plays a variety of roles in healthy dividing cells, it is not important for normal liver cell growth and regeneration. In fact, the Myc gene can be completely deleted from normal liver cells without affecting their long-term regenerative potential, as Dr. Prochownik and his colleagues reported in other work earlier this year.

In the current study, researchers studied the gene’s role in a mouse model of hepatoblastoma, a form of liver cancer that occurs in children, typically under the age of 3. Using genetic engineering techniques, the team induced hepatoblastoma tumors in mice that either did or did not have Myc in their liver cells. They found that mice lacking Myc in their liver cells generated tumors more slowly and survived longer than expected.

“Mice lacking liver Myc still developed tumors, but the tumors grew more slowly, suggesting that tumor growth, but not initiation, is dependent on Myc,” explained Dr. Prochownik.

Subsequent experiments showed that Myc promotes tumor growth by turning up the cell’s thermostat, raising its rate of metabolism so it can supply all of the metabolic building blocks and energy needed for rapid tumor growth. Prochownik and his colleagues believe that the different needs for Myc in normal versus tumor growth may be due to the fact that, in the latter case, this “metabolic thermostat” is turned up higher and therefore is more Myc-dependent. The more controlled conditions that exist with normal liver regeneration are therefore much less Myc-dependent.

Given that Myc plays such an important role in many cancers, a drug that inhibits it is an attractive therapeutic, explained Dr. Prochownik. However, because Myc is expressed in normal cells as well as cancerous ones, there have been concerns in the field that inhibiting the gene would produce too many detrimental side effects.

“Our research strongly suggests that this is not the case. Normal cells are not dependent on Myc the way that tumor cells are, so a Myc inhibitor could selectively target cancer cells while sparing healthy cells,” he added.

Over the past several years the team has developed several Myc inhibitors and they are now working to improve the drugs’ efficacy in cell culture and animal models of cancer. So far, they are proving to be effective in models of multiple myeloma and neuroblastoma, Dr. Prochownik said.

“Although they are not quite ready to give to patients yet, these compounds are a very exciting approach to treating a variety of cancers,” he added.

This research was supported by National Institutes of Health grants 5RO1 CA174713, 1R01 CA204586, and 1R01 DK100287.

Additional co-authors of the new paper include Huabo Wang, PhD, Jie Lu, BS, Lia R. Edmunds, PhD, Sucheta Kulkarni, PhD, James Dolezal, BA, Junyan Tao, PhD, Sarangarajan Ranganathan, MD, Laura Jackson, MD, Marc Fromherz, BA, Donna Beer Stolz, PhD, Radha Uppala, BS, Sivakama Bharathi, PhD, Satdarshan P. Monga, MD, and Eric S. Goetzman, PhD, all of the University of Pittsburgh.

2017 Society of Robotic Surgery Meeting

Call for abstracts and registration are Now Open for the 2017 Society of Robotic Surgery Meeting. This year’s meeting is being held at The Hilton Miami Downtown from February 24-26, 2017.

The SRS 2017 Annual Meeting will be a comprehensive robotic symposium featuring internationally-renowned faculty who are dedicated experts in their fields of study. The meeting will feature step-by-step techniques with in-depth commentary by the world’s leading robotic surgeons. This meeting is for everyone from surgeons new to robotic surgery, to first assists, as well as advanced robotic surgeons who want to improve their techniques.

The conference features presentations by leading experts in robotic surgery and will include specialty breakout sessions for:
o    Colorectal
o    ENT
o    General Surgery
o    Gynecology
o    Hernia & Single Site
o    Pediatric
o    Thoracic & Cardiac
o    Urology

See the latest advancements in robotic surgery with video sessions that are panel-narrated by leading faculty in the field with detailed procedural overviews. In addition, attendees of this three-day program will learn the latest advances in robotic surgery and have the opportunity to register for hands-on simulation courses.

This year’s Co-Chairs for the meeting are Dr. Uma Duvvuri-Assistant Professor, Director of Robotic Surgery, Department of Otolaryngology University of Pittsburgh School of Medicine and Dr. Jason Newman-Associate Professor Otorhinolaryngology- Head and Neck Surgery Center for Cranial Base Surgery University of Pennsylvania.

Uma Duvvuri, MD, PhD

Uma Duvvuri, MD, PhD

 

2017 Conference Highlights:
•    Tips & tricks in robotic urology
•    Up-to-date scientific data on oncological and functional outcomes
•    Hands-on training
•    What is new in robotics?
•    What is the advantage of the da Vinci Xi in urological practice?
•    Weekend of the Miami Food Festival

For Further registration information and to submit an abstract, go to www.srobotics.org.

Grant Awarded for National Biorepository for GUDMAP Biobank

Sunder Sims-Lucas, PhD, and Jacqueline Ho, MD, are co-investigators on a $600,000 per year grant for 5 years from the National Institutes of Health to be the national biorepository for the GenitoUrinary Development Molecular Anatomy Project (GUDMAP).

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GUDMAP is an international consortium working to generate gene expression data and transgenic mice as tools to study genitourinary development. This curated, high-resolution dataset serves as a powerful resource for biologists, clinicians and bioinformaticians interested in the developing urogenital system.

GUDMAP data is accessible at www.gudmap.org.

Hospitalized Patients at Risk if Sodium Levels are Low

Michael Moritz, MD, explains how hospitalized patients could be at risk of weak bones, and increased infections if physicians ignore low-sodium in the body, known as hyponatremia.

Dr. Moritz is clinical director, Division of Pediatric Nephrology at Children’s Hospital of UPMC and as Professor of Pediatrics at the University of Pittsburgh School of Medicine. Dr. Moritz is an authority on sodium and water metabolism in children.

Hospitalized patients at risk if sodium levels are low – Frontiers Science Hero from Frontiers on Vimeo.

Growing Kidneys in Lymph Nodes

Carl Bates, MD, and Sunder Sims-Lucas, PhD, of the Division of Pediatric Nephrology at Children’s Hospital of Pittsburgh of UPMC, in collaboration with Eric Lagasse, PhD, of the University of Pittsburgh McGowan Institute for Regenerative Medicine, are developing a novel approach to regenerate kidney tissues.

The group has discovered that embryonic kidney fragments and isolated nephron progenitors have the potential to form perfused kidney structures when injected into mouse lymph nodes. The Bates, Sims-Lucas, and Lagasse laboratories have received a Pediatric Device Initiative Award sponsored by the Commonwealth of Pennsylvania in support of their work.

 

Dr. Charles Reynolds wins 2016 Pardes Humanitarian Prize in Mental Heath

The Brain & Behavior Research Foundation recently announced Charles F. Reynolds, III, MD, as one of the winners of the 2016 Pardes Humanitarian Prize in Mental Health. Dr. Reynolds was recognized for pioneering work in geriatric psychiatry and treatment of late-life depression. Dr. Reynolds’ fellow 2016 Parades winners included Vikram Patel, PhD, F Med Sci, for transformative work in advancing mental health care in resource-poor countries. and an Honorary Tribute to the late Senator Edward M. Kennedy for his powerful and unwavering commitment to advocating on behalf of people with mental illness.

The Pardes Humanitarian Prize in Mental Health is awarded annually to recognize individuals whose contributions have made a profound and lasting impact in advancing the understanding of mental health and improving the lives of people suffering from mental illness. It focuses public attention on the burden mental illness places on individuals and society, and the urgent need to expand mental health services globally. Established in 2014, The Pardes Humanitarian Prize in Mental Health is named in honor of Herbert Pardes, MD, a noted psychiatrist, advocate for the mentally ill, and the award’s first recipient.

Dr. Reynolds 2016 Pardes Humanitarian Prizewinner Video

“The 2016 Pardes Prize recipients have applied their scientific knowledge, deep understanding of human behavior and compassion to improve the lives of millions of people suffering from mental illness, especially those living in poverty,” said Dr. Pardes, President of the Brain & Behavior Research Foundation’s Scientific Council and Executive Vice Chair of the Board of Trustees at NewYork-Presbyterian Hospital. “Their work has expanded our scope of mental illness treatment around the world. They have taught us about the needs of our diverse human family and how to use knowledge for the greater good of humanity.”

Dr. Pardes added, “Dr. Patel and Dr. Reynolds exemplify what it means to be a humanitarian.  Dr. Patel’s mission is to bring desperately needed psychiatric care to people living in countries where access to these services is limited or non-existent. Dr. Reynolds is a pioneer in geriatric psychiatry whose mission is to help the elderly lead full and productive lives in their later years.   We honor them both for their outstanding commitment to alleviating the pain and suffering of mental illness.”

Dr. Reynolds and his colleagues have made groundbreaking contributions to the prevention and treatment of depression in older adults. Depression has been identified by the World Health Organization as a leading cause of disability worldwide and a major contributor to the global burden of disease across the life cycle.

Dr. Reynolds helped to define a new global health priority as depression prevention in older adults, now recognized as a feasible public health goal. He and his colleagues have also demonstrated that depression treatment reduces both suicidal risk and cancer-related mortality risk in elderly medical patients, and his work has informed long-term treatment strategies to prevent recurrence and to delay dementia in depression with mild cognitive impairment.

Dr. Reynolds leads an NIMH study with the Goa Medical College/India and with Sangath to develop and test a scalable model of depression prevention. Building upon the contribution of Pardes Prize co-recipient Dr. Vikram Patel, this work uses lay health counselors for early intervention in mildly symptomatic older adults, thereby optimizing scarce mental health resources to prevent depression onset. The NIMH-sponsored center in late life mood disorders, which Dr. Reynolds directs at the University of Pittsburgh School of Medicine, has mentored 25 research-career development (NIH K) awardees since 1995.

In addition to co-founding the Global Consortium on Depression Prevention and editing the American Journal of Geriatric Psychiatry, Dr. Reynolds has served as president of the American College of Psychiatrists, the International College for Geriatric Psychoneuropharmacology, the American Association for Geriatric Psychiatry, and the American Foundation for Suicide Prevention. He has received the APA Weinberg Award for lifetime contributions in geriatric psychiatry, the American College of Psychiatrists’ research award in geriatrics, the International Psychogeriatric Association lifetime service award, and the Exemplary Psychiatrist Award from the National Alliance for the Mentally Ill.

“It is a privilege and an honor to be a recipient of the Pardes Humanitarian Prize. In our youth-focused culture, the elderly and their struggles with mental illness are often overlooked and neglected. Late-life depression is a global health priority that has immense impact on older individuals and their families. It is my sincere hope that as a society we can work to restore the joy of living to older adults affected by mental illness,” Dr. Reynolds said.

Advances in Inflammatory Bowel Diseases Conference 2016

The 2016 Advances in Inflammatory Bowel Diseases Conference (AIBD) is being held December 8-10, 2016 in Orlando.

This event will showcase emerging treatment options including therapies and surgical management as well as advancements in quality of care in the field of IBD, and presentations and keynote speeches from experts who are leaders in their field.

Several UPMC faculty and staff will speak on a number of topics including:

CLINICAL ORGANIZING COMMITTEE MEMBERS:                               

Sandra Kim, MD
Miguel Regueiro, MD

MEET THE EXPERTS LUNCHEONS

 December 9, 2016: Can we better position biologics to optimize the management of Crohn’s disease?
Miguel Regueiro, MD

 December 10, 2016: An under-recognized ‘extra-intestinal’ manifestation of IBD: how best to manage stress, anxiety, and depression in our IBD patients.
Eva Szigethy, MD, PhD

 CLINICAL TRACK AGENDA
December 8, 2016: Session II-A: Current Therapeutic Approaches for the Optimal Medical Management of IBD

3:40 pm What will be the hot IBD clinical topics in 2017?
Miguel Regueiro, MD

Session Track V-A: Challenges in IBD: Case discussions

Moderators: Miguel Regueiro, MD, Corey A. Siegel, MD, MS
10:30 to 12:30 pm

December 9, 2016: Session VI-A: Case-based Clinical Breakout Sessions
Presented at both 2:00 and 3:00 pm

New models of care for IBD: The patient centered medical home and increasing patient engagement: Case studies
Miguel Regueiro, MD, Eva Szigethy, MD, PhD, Corey A. Siegel, MD, MS

December 10, 2016: Session VIII-A: Advances in the Care of IBD Patients

8:40 am Is there an optimal approach to prevent recurrence in post-operative Crohn’s disease?
Miguel Regueiro, MD

9:00 am Approaches used to avoid and treat narcotic dependence
Eva Szigethy, MD, PhD

PEDIATRIC TRACK AGENDA
December 9, 2016: Session VI-D: Progress in Pediatric IBD

Moderators: Sandra C. Kim, MD, Francisco A Sylvester, MD
2:00 to 4:00 pm
and
2:20 pm Extraintestinal manifestations in pediatric IBD – a survey of conditions and treatments: Rheumatologic manifestations
Sandra C. Kim, MD

Session VII-D: Advances in Pediatric IBD

5:00 pm Case discussions with expert 5 person panel
Panelists: Sandra C. Kim, MD, Millie D. Long, MD, MPH, Francisco A. Sylvester, MD

December 10, 2016: Session VIII-D: Common Clinical Challenges in Pediatric IBD

9:00 am What are effective approaches to counsel our pediatric IBD patients, who are undergoing surgery for Crohn’s disease or ulcerative colitis?
Sandra C. Kim, MD

 Session IX-D: Targeting Therapies for the Pediatric Patient

11:10 am Topics in ulcerative colitis
Panelists: Athos Bousvaros, MD, MPH, Sandra C. Kim, MD, Francisco A. Sylvester, MD

Center for Advanced Robotics Training Thoracic Surgery Course — December 9-10, 2016

December 9-10, 2016

Overview:

The Center for Advanced Robotics Training (CART) program in thoracic surgery offers an in-depth introduction to advanced pulmonary, mediastinal, and esophageal procedures, including lobectomy, thymectomy, and esophagectomy. Instructed by leaders in the field of minimally invasive thoracic surgery, the program features individualized didactic and hands-on experience, including overview of the operating suite setup, review of equipment and instruments, and step-by-step guidance in performing critical aspects of these complex procedures through simulation and cadaver work. The course offerings are highly customizable to address the specific procedural interest, skill level, and needs of each participant.

Day One: December 9

7 a.m. Introduction to CART 8 a.m. Observation of Live

Surgery

12 p.m. Lunch

1 p.m. Simulation Lab Sessions

5 p.m. Review of Curriculum Pathway and Practical Skill Session Goals

7 p.m. Working Dinner with Step-by-Step Technical Video Presentation

9:00 p.m. Adjourn

Day Two: December 10

7 a.m. Breakfast

8 a.m. Robotic Practical Skills Cadaver Lab #1

12 p.m. Lunch

1 p.m. Simulation Lab Session

3 p.m. Robotic Practical Skills Cadaver Lab #2

Cost: $4,000/surgeon

Maximum attendance: 4 surgeons

For more information, please contact:

Daniel Battista, MBA, Administrative Director

UPMC Center for Advanced Robotics Training (CART) UPMCRoboticTrainingCenter@upmc.edu

1-844-304-2278

UPMC.com/CART

Center for Advanced Robotics Training Complex Pancreatic Resections Course — December 15-16, 2016

December 15-16, 2016

Overview:

This course will serve as an introduction to the advanced robotic curriculum, and will also expose participants to the skill sets necessary to safely perform advanced robotic pancreatic resections. The UPMC Robotic Hepatobiliary and Pancreatic Surgery (HPB) program under the direction of Dr. David Bartlett and Dr. Herbert Zeh is a highly accomplished surgical program. This team has performed over 600 major pancreatic and liver resections, including nearly 300 pancreaticoduodenectomies and more than 100 robotic liver resections. They have published a number of highly-cited articles in this field. Over the last several years, this program has dedicated significant resources to developing a comprehensive proficiency-based curriculum for advanced robotic skills.

Day One: December 15

7 a.m. Case Observation (Robotic Whipple*)

3 p.m. Didactic Session

Robotic nurse coordinator

Robotic distal pancreatectomy

Robotic pancreaticoduodenectomy

Overview of robotic simulation and training curriculum

Overview of biotissue drills/testing

6 p.m. Working Dinner

Video presentations: scope of robotic HPB cases

Day Two: December 16

7 a.m. Continental Breakfast

8 a.m. – 12 p.m. Simulator/ Inanimate and Biotissue Skill Evaluations

12 – 1 p.m. Lunch

1 – 4 p.m. Cadaver Lab

*If surgical procedure is cancelled due to unforeseen circumstances, a previously recorded full-length procedure will be used for discussion

Cost: $4,000/surgeon

Maximum attendance: 6 surgeons

This activity has been approved for AMA PRA Category 1 Credit(s)™

 

For more information, please contact:

Daniel Battista, MBA, Administrative Director

UPMC Center for Advanced Robotics Training (CART) UPMCRoboticTrainingCenter@upmc.edu

1-844-304-227

MidAtlantic AIDS Education and Training Center Hosts World AIDS Day 2016 Conference

WHAT: To observe the 28th World AIDS Day, The MidAtlantic AIDS Education and Training Center (MAAETC), based at the University of Pittsburgh Graduate School of Public Health, will collaborate with UPMC and local HIV/AIDS clinics to host an all-day educational event. The World AIDS Day 2016 conference will bring together experts in the field of HIV to enable physicians, nurses and other HIV care providers to improve care. Experts will discuss prevention including PreP, aging and HIV, antiretroviral treatment, and substance use and HIV.

To learn more or register, visit https://www.maaetc.org/events/view/8202.

WHY: Despite advances in HIV treatment, there continues to be an increase in HIV infections. This necessitates routine testing for everyone, to identify and link persons with HIV to care so that they can live longer lives. New treatment is available to prevent HIV infection, and concerns and issues are emerging among persons aging with HIV infection.

WHO:

• Introductions by Corey O’Connor, councilman, City of Pittsburgh, and Donald S. Burke, MD, Dean, Pitt Public Health.

• Speakers include:

o Rachel Levine, MD, physician general, Commonwealth of Pennsylvania
o Harold Wiesenfeld, MD, MPH, Allegheny County Health Department, and Magee-Womens Hospital of UPMC
o Donna Gallagher, PhD, MSN, ANP-BC, FAAN,
New England AIDS Education and Training Center
o Ken Ho, MD, MPH, medical director, Pitt Men’s Study,
University of Pittsburgh School of Medicine
o Antoine Douaihy, MD, medical director, Addiction Medicine,
University of Pittsburgh Department of Psychiatry

WHEN: 8:30 a.m. to 5:30 p.m., Thursday, Dec. 1

WHERE: University Club, 123 University Place, Pittsburgh, 15260

Note to Media: To cover this event, contact Allison Hydzik at 412-647-9975 or HydzikAM@upmc.edu.

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