September, 2008 Update - CCF Research
September, 2003 Update - Friendly Terms
September, 2003 Update - Medical Terms
2003: Studies in solid tumors with poor-prognosis
2003: Additional Research
2001: Studies In Leukemia:
2001: Studies in Solid Tumors:

September, 2008 Update - CCF Research
A 2008 UPDATE ON CCF RESEARCH IN THE CHILDREN'S CANCER RESEARCH LAB

For the past two years, Dr. GyeongHun Baeg and his associates at the Children’s Cancer Research Lab have been working to identify chemical and plant compounds that will selectively inhibit cancer cells (without affecting normal cells). The following is an abstract of his work that will be published this month (September 2008).

Cancer cells divide indefinitely because of inappropriate activation of certain proteins that send signals to the nucleus of the cells to continue divide. One such pathway is called JAK/STAT signaling which is activated in many human cancers. Therefore, the development of drugs that inhibit this pathway will be very useful in the treatment of human cancers. Using Drosophila (fruit fly) as a model organism, Dr. GyeongHun Baeg and his associates at Children’s Cancer Research Laboratory at New York Medical College have identified AUH-6-96 as a novel compound that inhibits JAK/STAT signaling in humans. This reagent selectively affected cell viability only of cancer cells harboring aberrant JAK/STAT signaling by inducing apoptosis via down-regulating the expression of STAT downstream target anti-apoptotic genes. Importantly, this study shows that AUH-6-96 may have therapeutic potential in the treatment of human cancers harboring constitutively-active JAK/STAT signaling. This finding will be introduced in the September issue of Molecular Cancer Therapeutics that is published by the American Association for Cancer Research, Inc.

The next step in his research is to learn if this JAKSTAT pathway is activated in certain pediatric cancers. Dr. Claudio Sandoval and Dr. Baeg will be collaborating in a study described below, and will be started soon.

Drs. GyeongHun Beg, Claudio Sandoval and S. Jayabose - The Children's Cancer Research Laboratory August 12, 2008

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September, 2003 Update - Friendly Terms
SIGNIFICANCE OF RESIDUAL LEUKEMIA IN THE BONE MARROW AND CEREBROSPINAL FLUID IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Acute Lymphoblastic Leukemia (ALL) is the most common form of cancer in children, in which lymphoblasts (the immature form of normal white blood cells) become malignant. Each year about 2,000 children in the United States develop ALL, and only 80% of them are being cured. The most common obstacle is having the cancer come back, called a relapse. With currently available techniques we are only able to detect leukemia cells in the bone marrow when there are more than 5 leukemia cells in every 100 cells. (Bone marrow is the soft tissue in the hollow of flat bones of the body that produces new blood cells.) The presence of leukemia cells below this detection limit is termed Minimal Residual Disease (MRD). We recently developed a new technique called real-time polymerase chain reaction (PCR) that is capable of detecting MRD as low as 1 leukemia cell in 20,000 cells.

Studies have shown (both in our lab and by others) that studying MRD in a patient's bone marrow and/or cerebrospinal fluid may predict which patients are at risk of having a relapse. (Cerebrospinal fluid is the watery fluid that surrounds the brain and spinal cord.) We have spent many years fine-tuning a PCR methodology that can be used to test a large number of patients in a short amount of time. The more patients we can test, the faster we know if our method can reliably predict relapse. In this study, we will test the bone marrow and spinal fluid from 1200 children who are in remission. The children who participate on this study will be from all over the United States, Canada and Australia, and they will be treated at their local hospital. At certain times during remission, the primary physician will draw bone marrow and/or spinal fluid and mail the samples to our laboratory. We will not know the name or clinical status of the child because the samples only have a code number to identify them. We will collect our test results until all the patients have been tested, and then analyze the results altogether.

We expect that after this study we will know whether we can predict relapse using our method. Our long-term goal is to significantly reduce the number of children who relapse by treating all patients according to how their individual leukemia responds to chemotherapy. We hope the results will help us in the future to reduce the amount of treatment in those children whose leukemia disappears quickly, and increase treatment in those children whose leukemia persists during chemotherapy.

Sharon R. Pine, Ph.D. - The Children's Cancer Research Laboratory September 15, 2003

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September, 2003 Update - Medical Terms
Dr. Sharon Pine of the Children's Cancer Research Laboratory and the Pediatric Hematology-Oncologists at New York Medical College, in collaboration with the University of California, San Francisco, are exploring the origins of childhood leukemia. They discovered that the two most common genetic changes in childhood leukemia occur by two different mechanisms, which has a large impact in understanding the cause of leukemia. Secondly they discovered that some genetic changes occur even before the child is born, but others take place after birth. Their work has been published in the Proceedings of the National Academy of Science (2002) and Leukemia Research (2003).

Dr. Sharon Pine's persistence in optimizing a simplified test to detect residual leukemia during remission has earned the Children's Cancer Research Laboratory national recognition. This work was published in the Journal of Pediatric Hematology-Oncology (2003). Under the direction of S. Jayabose, M.D., researchers in the laboratory, including Sharon R. Pine, Ph.D., ChangHong Yin, M.D., QianXu Guo, M.D., and Kristen Kellock, are running a national study to determine if residual leukemia detection early in therapy can predict leukemia relapse. This study is being conducted in collaboration with the Children's Oncology Group---with the participation of most major medical centers in the United States and medical centers in Canada and Australia.

Over 200 patients have been enrolled so far and an additional 300 patients will be entered on the study by early 2005. A preliminary report was presented to the Children's Oncology Group in the April 2003 meeting in St Louis, MO. The Group was most impressed with the report on detecting residual leukemia in cerebrospinal fluid, a source of relapse in some children. A manuscript on the cerebrospinal fluid data is currently being drafted. The patients need to be followed for at least four years before the final results of the study can be analyzed. The results of this study will most likely enable the identification of children at higher risk of relapse, even at the early stages of treatment, so that they can be treated more intensively and relapses in ALL can be avoided.

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2001: Studies In Le ukemia: The Children's Cancer Research Laboratory of New York Medical College has been conducting studies on minimal residual disease (MRD) in children with acute lymphoblastic leukemia (ALL) for the past several years. We have recently achieved two important milestones:

1. We have optimized a new methodology called real-time PCR for testing MRD, and we are submitting our work for publication in a peer-reviewed journal Cancer Research. This real-time PCR technique shortens the time it takes to get test results, which in turn, will allow us to perform studies on a larger number of patients.
   
   
2. We are about to start a large MRD study in collaboration with the Children's Oncology Group. This is a national organization for research in childhood cancers. Sharon Mayer, Associate Director of the Children's Cancer Research Laboratory, will be the co-chair of this study. We will be studying a total of 1200 children with ALL over a period of 2 1/2 years. This study will determine if we can predict which child will be at a very high risk for relapse, even in the early stages of treatment. This is a crucial study. If we can predict who will relapse, we can intensify treatment to prevent relapse. Thus, studies in our laboratory will help improve the cure rate for all children with ALL. Because of the large number of children we will be studying, this project will be an expensive one, and we are indebted to CCF and its supporters for making this research project possible.

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2001: Studies in Solid Tumors:

1. Dr. Fevzi Ozkaynak, Director of Pediatric Blood and Bone Marrow Transplant Program is conducting two studies on a very selected group of patients who have little chance of cure. These are patients who have relapsed solid tumors or advanced disease that are resistant to ordinary chemotherapy. Very high dose therapy, followed by stem cell transplantation, is often necessary in these patients in order to eradicate resistant cancer cells. However, the success of such high dose therapy has been thus far compromised by excessive toxicity of the chemotherapy itself. Dr. Ozkaynak's first study aims to find out if by using a drug called amifostine one can prevent the toxicity of very high dose chemotherapy. This research is being done in collaboration with many other major centers. He has studied 21 patients and the early results are very encouraging.
   
   
2. In a second study, Dr.Ozkaynak is exploring the feasibility of giving multiple courses of very high-dose chemotherapy with peripheral blood stem cell support in relapsed, refractory or progressive pediatric solid tumors. This study is also being done in collaboration with other centers. So far ten patients have been studied. The results on the initial eight patients were reported at the Twelfth Annual Meeting of the American Society of Pediatric Hematology/Oncology (ASPHO), September 1999. Dr. Ozkaynak hopes to complete these two studies in approximately two years.

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