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Highlights - Promise, Autumn 2011


Highlights - Promise, Summer 2011

 



Embracing the future

St. Jude Pediatric Oncology Education (POE) program director Suzanne Gronemeyer, PhD, receives a group hug from some of the 2011 POE participants (from left) Aaron Deleonguerrero, Erika Russell, Ronald Rodriguez-Santiago, Ronald Valencia, Alexandra Rivera-Santiago, Krystal Herline and Corianne Rogers.

POE students Funded by the National Institutes of Health/National Cancer Institute, the POE program provides students with short-term internships in laboratory or clinical research.

The POE program received more than 550 applications this year for 50 openings in its summer 2011 program for students interested in making cancer the centerpiece of their professional lives.

“The success of future biomedical research depends on the availability of well-trained young investigators. There is a shortage in both the number and diversity of well-trained, competent pediatric oncology researchers, clinicians and nurses in this country,” Gronemeyer said. She recently authored a report on the St. Jude POE program, which appeared in the Journal of Cancer Education.

To learn more about the program, visit www.stjude.org/poe.

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A dramatic increase in transplant surviaval

Bone marrow transplant survival more than doubled in recent years for children with high-risk leukemia treated at St. Jude, with patients lacking genetically matched donors recording the most significant gains. The results are believed to be the best ever reported for leukemia patients who underwent the procedure.

The findings are expected to make transplantation a treatment option for more children and adolescents with high-risk forms of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) who lack genetically matched donors, either related or unrelated. The research appeared in the scientific journal Blood.

“This study shows that transplantation offers a real hope of survival to patients with high-risk leukemia that is not curable with intensive chemotherapy,” said Wing Leung, MD, PhD, the study’s principal investigator and chair of Bone Marrow Transplantation and Cellular Therapy. Leung linked the gains to advances in cancer treatment as well as to improved infection control and more sophisticated donor selection.

Five years after transplantation, survival was 65 percent for St. Jude patients with high-risk ALL treated at the hospital between 2000 and 2007, compared to 28 percent for similar patients who underwent treatment between 1991 and 1999. AML survival after transplantation rose from 34 percent for patients treated between 1997 and 2002 to 74 percent for the AML patients treated between 2002 and 2008.

“We can now identify donors for virtually all pediatric patients who need transplants to cure their leukemia. Importantly, our transplanted patients not only have high cure rates but also excellent quality of life, resulting largely from advances in donor selection and supportive care,” said Ching-Hon Pui, MD, Oncology chair and the paper’s senior author.

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Regulating immune balance

St. Jude researchers are constantly seeking new ways to help patients’ own immune systems effectively fight disease. Now, investigators have identified a signaling molecule that functions like a factory supervisorSt. Jude researchersto ensure that the right mix of specialized T cells is available to fight infections and guard against autoimmune disease. The research also showed the molecule, phosphatase MKP-1, is an important regulator of immune balance. Scientists demonstrated that MKP-1 serves as a bridge between the innate immune response that is the body’s first line of defense against infection and the more specialized adaptive immune response that follows. A report on this study appeared in the journal Immunity.

The results raise hopes that the MKP-1 pathway will lead to new tools for shaping the immune response, said the study’s senior author, Hongbo Chi, PhD, of Immunology. Chi (seated, second from left) is joined by (from left) the study’s co-first authors, postdoctoral fellows Yanyan Wang, PhD, and Gonghua Huang, PhD; and additional author Lewis Shi, MD, PhD. The findings provide new details about how dendritic cells regulate the fate of naïve or undifferentiated T cells. Dendritic cells patrol the body, ready to respond at the first sign of infection.

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Sibling Star DayStar power unleashed

Amanda Koziol, whose sister is undergoing leukemia treatment at St. Jude, takes a red carpet walk past cheering doctors, nurses and other staff during Sibling Star Day. The annual event held for the brothers and sisters of patients celebrates and recognizes the important role siblings play in the healing process. This year’s event, themed “Hollywood,” featured arts-and-crafts, a luncheon for siblings and other special activities.

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Finding order in chaos

A key finding by St. Jude researchers could lead to a new family of cancer drugs.

Investigators in the project identified the structure responsible for the versatility of a protein called p21, which belongs to a class of proteins known as intrinsically disordered proteins (IDPs). Unlike many other proteins, which form rigid 3-D shapes and bind to single partners, IDPs are unstructured, which allows them to fold, binding to different partners and performing diverse biological tasks.

Disordered proteins are often altered in cancer, affecting many regulatory and signaling pathways. Tumor suppressor proteins frequently include disordered segments. Researchers showed that p21’s structural flexibility is essential to its ability to bind to and inhibit several different enzyme complexes that regulate cell division.

“Disordered proteins hold great potential for understanding the molecular basis of cancer,” said Richard Kriwacki, PhD, of Structural Biology. The proteins also represent challenging new targets for small-molecule inhibitors to block their regulatory interactions.

Kriwacki is senior author of a paper on this topic, which was published in the journal Nature Chemical Biology.

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Teamwork yields targeted AML therapy

A drug that targets a molecular misstep at the heart of 15 percent of childhood acute myeloid leukemia (AML) cases has shown early promise in a safety study led by St. Jude researchers and is now being tried in newly diagnosed patients.

In eight of 11 young AML patients enrolled in a St. Jude Phase I study, cancer went into remission following treatment with a drug named sorafenib and two other chemotherapy agents. A ninth patient had a partial remission. The patients had all relapsed or failed to respond to earlier therapies. The research appeared in the Journal of Clinical Oncology.

If results are confirmed in larger studies, sorafenib will mark a new era in treatment of AML, said the study’s first author, Hiroto Inaba, MD, PhD, of Oncology. Inaba said sorafenib is a good example of close collaboration between St. Jude researchers in the laboratory and clinic. He said work from the laboratory of Sharyn Baker, PharmD, PhD, of Pharmaceutical Sciences, provided the foundation for the Phase I study. Baker is the study’s senior author.

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New target pinpointed for eye tumor

A research team led by St. Jude scientists has identified a potential new target for treatment of the childhood eye tumor retinoblastoma. The work also settles a scientific debate by showing that the cancer’s cellular origins are as scrambled as the developmental pathways at work in the tumor.

Unlike other cancers that resemble a particular type of cell, researchers showed that retinoblastoma is a hybrid cell with elements of at least three different cell types. The research appeared in the scientific journal Cancer Cell. Researchers also demonstrated that multiple, normally incompatible, developmental pathways are turned on simultaneously in retinoblastoma cells. The study found the tumor takes over at least one pathway to fuel its own growth, making it a promising drug development target.

The study’s senior author is Michael Dyer, PhD, of Developmental Neurobiology.

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St. Jude more than doubles national vaccination rates

St. Jude investigators recently published results of the first study to report employee attitudes about influenza vaccine at an institution with high rates of voluntary vaccination.

Flu shotsMore than 90 percent of St. Jude health care workers are voluntarily vaccinated against influenza each year. That number is in sharp contrast to national vaccination rates—about 44 percent of health care workers nationwide receive flu vaccinations each year. Investigators found that altruism and self-protection both play a role in the high St. Jude rates.

Scott Howard, MD (above), of Oncology and Information Sciences, receives his annual flu shot as part of the hospital’s vaccination program.

The findings, published in the journal Vaccine, demonstrate that high rates of flu vaccination are possible without making vaccination of health care workers mandatory, said Hana Hakim, MD, of Infectious Diseases, the study’s principal investigator. But she noted that the hospital’s patient population and its mission make it difficult to generalize the findings to other health care settings. Jon McCullers, MD, of Infectious Diseases, was the paper’s senior author.

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Talking to children about prayer

Using feedback from parents of St. Jude patients, Chaplain Services has developed a book to help parents incorporate prayer into their children’s hospital experience. The project began when members of the St. Jude Family Advisory Council observed that many parents Talking to children about prayeracknowledged having difficulty talking about prayer with their children. To help facilitate those conversations, Chaplain Services wrote Sometimes A Prayer for children ages 3 to 8.

“Even under normal circumstances, prayer can be a tough concept for young children,” said Brent Powell, Chaplain Services director. “After discussing the topic with parents, the chaplains agreed that the best way to help both parents and children was to properly equip the parents, since they are usually available to the children and have the most trusted relationship.”

Chaplain Mark Brown (above) shares the new book with St. Jude patient Haley Hines.

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New hope for children with solid tumors

A drug that blocks a pathway commonly disrupted in cancer has shown early promise against childhood solid tumors and is now being combined with other agents in a Phase II trial targeting rhabdomyosarcoma, the most common soft tissue cancer of childhood.

The drug is temsirolimus. In a Phase I study, a child’s neuroblastoma tumor disappeared completely for about nine months in response to weekly intravenous treatments with the drug. The disease stabilized in five patients with other childhood cancers. All had undergone prior therapy that failed to eradicate their disease.

The results were published in the Journal of Clinical Oncology. Sheri Spunt, MD, of Oncology, was principal investigator of a multi-center trial that focused on the safety and optimal dose of temsirolimus in young solid tumor patients.

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Assessing survivors’ risks

The largest study yet of adult childhood cancer survivors found that, for some survivors, the first cancer was just the beginning of a lifelong battle against different forms of the disease. The work underscores the importance of cancer screenings for the estimated 366,000 Americans alive today who are childhood cancer survivors.

St. Jude investigators led the study involving 14,358 individuals enrolled in the Childhood Cancer Survivor Study. Researchers reported that nearly 10 percent of survivors developed new tumors unrelated to their original cancers. About 30 percent of those survivors developed three or more tumors. Results of the study appeared in the Journal of Clinical Oncology.

“These findings show that when you describe adult survivors of childhood cancer it is not sufficient to describe their risk of a first subsequent cancer, but to acknowledge that some of these patients are at risk for multiple cancers. This is the first study to more fully enumerate that risk,” said principal investigator Gregory Armstrong, MD, of Epidemiology and Cancer Control.

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A glimpse into the immune system

St. Jude scientists have identified a key immune system regulator, a protein that serves as a gatekeeper in the white blood cells that produce the “troops” to battle specific infections.

Researchers demonstrated the protein, Tsc1, is pivotal for maintaining a balanced immune system and combating infections. Loss of the Tsc1 protein was associated with a reduction in the number of certain immune cells and a weaker immune response. A report on this work appeared in the scientific journal Nature Immunology.

“These findings not only advance understanding of the cell biology of the immune system but also have great potential for clinical applications in the future,” said the study’s senior author, Hongbo Chi, PhD, of Immunology.

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Scientists learn how Sudemycins work

St. Jude scientists have collaborated to show that a promising family of anti-cancer drugs, known as Sudemycins, works by influencing how a cell’s machinery edits messenger RNA (mRNA).

Researchers reported that mRNAs that code for proteins made by a mechanism called alternative splicing change in response to treatment with this family of antitumor drugs. Alternative splicing determines how information encoded in DNA is packaged to produce different versions of mRNA that is then translated to produce variants of the encoded protein. The process makes it possible for a single gene to yield multiple, related proteins. Other scientists have demonstrated that alternate splicing is deregulated in many cancers.

The laboratories of Philip Potter, PhD, and Thomas Webb, PhD, both of Chemical Biology and Therapeutics, worked together to understand the biology that makes Sudemycins such promising anti-cancer drugs. Webb had previously discovered Sudemycins at St. Jude. The most recent research appeared in the journal ACS Chemical Biology.

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Science can be fun

Science can be funThe St. Jude Cancer Education for Children Program visited the St. Jude Adopt-A-School, Bellevue Middle School, recently for an outreach education event. Several St. Jude staff members discussed science careers with the school’s sixth and seventh grade students. Students also participated in an educational microscope lab exercise from the Cure4Kids for Kids outreach program. Emma Delva, PhD, of Immunology (at right), assists a Bellevue student with the exercise.

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Exploring the origins of devastating diseases

The enzyme ligase III (Lig3) has long been linked to fixing broken strands of DNA in the cell’s nucleus. But new work from the laboratory of Peter McKinnon, PhD, of Genetics, demonstrates that Lig3 makes its greatest contribution in the mitochondria, the energy-producing structures inside cells.

“We found that inactivating ligase III did not compromise nuclear DNA repair, but in a profound way it compromised mitochondrial DNA replication and repair. Defects in mitochondrial DNA lead to a spectrum of very different devastating childhood diseases,” explained McKinnon, senior author of a study that appeared in the journal Nature.

McKinnon said evidence suggests Lig3 might sometimes work cooperatively with Lig1, a related enzyme, to repair nuclear DNA damage. Efforts are underway to determine whether Lig3’s primary role is to keep mitochondrial DNA in good repair or to see that it is copied correctly.

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