Author Interviews, Cancer Research, Gastrointestinal Disease, Microbiome, Science / 27.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44863" align="alignleft" width="200"]Joao Xavier PhD Associate Faculty Member | Computational & Systems Biology Memorial Sloan Kettering Cancer Center New York, NY 10065 Dr. Joao Xavier[/caption] Joao Xavier PhD Associate Faculty Member | Computational & Systems Biology Memorial Sloan Kettering Cancer Center New York, NY 10065  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our team at Memorial Sloan Kettering has been investigating the intestinal microbiota of patients receiving bone marrow transplantations for more than eight years now. We have found through several studies that these patients lose important healthy bacteria from their microbiota, and that these losses are mostly caused by the antibiotics given as prophylaxis or to treat infections. We also found that the drastic changes in the microbiota composition, especially the intestinal dominations by bacteria such as Enterococcus, increase the risk of transplant-related complications and lowered patient survival. We aimed to determine the feasibility of autologous microbiota transplant (auto-FMT) as a way to reconstitute lost bacteria. This randomized study found that indeed auto-FMT could reconstitute important microbial groups to patients. 
Abuse and Neglect, Hematology, Lancet, Medical Imaging, Transplantation / 07.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40425" align="alignleft" width="133"]Kirsten Williams, M.D. Blood and marrow transplant specialist Children’s National Health System Dr. Williams[/caption] Kirsten Williams, M.D. Blood and marrow transplant specialist Children’s National Health System  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This study addressed a life-threatening complication of bone marrow transplantation called bone marrow failure. Bone marrow transplantation has provided a cure for patients with aggressive leukemias or acquired or genetic marrow dysfunction. The process of bone marrow transplantation involves giving chemotherapy and/or radiation, which removes the diseased blood cells from the bone marrow. After this, new bone marrow stem cells are infused from a healthy individual. They travel to the bone marrow and start the slow process of remaking the blood system. Because these new cells start from infancy, it takes upwards of four to five weeks for new mature healthy cells to emerge into the blood, where they can be identified. Historically, there has been no timely way to determine if the new cells have successfully repopulated unless they can be seen in the blood compartment. This condition of bone marrow failure is life-threatening, because patients don't have white blood cells to protect them from infection. Once bone marrow failure is diagnosed, a second new set of stem cells are infused, often after more chemotherapy is given. However, for many individuals this re-transplantation is too late, because severe infections can be fatal while waiting cells to recover. We were the first group to use a new imaging test to understand how the newly infused bone marrow cells develop inside the patient. We have recently published a way to detect the new bone marrow cell growth as early as five days after the cells are given. We used an investigational nuclear medicine test to reveal this early cell growth, which could be detected weeks before the cells appear in the blood. This radiology test is safe, does not cause any problems and is not invasive. It is called FLT (18F-fluorothymidine) and the contrast is taken up by dividing hematopoietic stem cells. The patients could even see the growth of their new cells inside the bone marrow (which they very much enjoyed while waiting to see recovery of the cells in their blood). We could use the brightness of the image (called SUV) to determine approximately how many weeks remained before the cells were visible in the blood. Finally, we actually could see where the new cells went after they were infused, tracking their settling in various organs and bones. Through this, we could see that cells did not travel directly to all of the bones right away as was previously thought, but rather first went to the liver and spleen, then to the mid-spine (thorax), then to the remainder of the spine and breastplate, and finally to the arms and legs. This pattern of bone marrow development is seen in healthy developing fetuses. In this case, it occurs in a similar pattern in adults undergoing bone marrow transplant.
Author Interviews, Transplantation / 16.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26937" align="alignleft" width="142"]Guo-fu Hu, PhD Investigator in the Molecular Oncology Research Institute Tufts Medical Center Dr. Guo-fu Hu[/caption] Guo-fu Hu, PhD Investigator in the Molecular Oncology Research Institute Tufts Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Angiogenin (ANG) is a ribonuclease that is known to promote cell growth and survival by differential processing of cellular RNAs. This paper reports three main findings.
  • 1) ANG has a cell type-specific role in regulating cell proliferation of the hematopoietic system: it promotes quiescence of the primitive hematopoietic stem/progenitor (HSPC) cells while simultaneously stimulating proliferation of more differentiated myeloid progenitor (MyePro) cells.
  • 2) ANG regulatesquiescence and proliferation of HSPC and MyePro through a novel mechanism: it induces tRNA-derived stress-induced small RNA (tiRNA) generation in HSPC and ribosomal RNA (rRNA) induction in MyePro, leading to respective reduction and increase in protein synthesis. To our knowledge, this is the first report of cell type specificity in RNA processing that leads to or originates from a different cellular state.
  • 3) Recombinant ANG protein is able to improve survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPC in transplantation, which have significant implication in a number of clinical situations including bone marrow failure and stem cell transplantations.
Author Interviews, Immunotherapy, Leukemia, Stem Cells, Transplantation / 12.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26960" align="alignleft" width="200"]Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016 Felix Garzon[/caption] Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016 MedicalResearch.com: What is the background for this study? What is goal of this Study? Response: Iomab-B (“Iomab”) was developed at the Fred Hutchinson Cancer Research Center (“the Hutch”) in Seattle, Washington. The Hutch is a pioneer in the field of bone marrow transplantation (BMT) having 3 Nobel Prizes and doctors there performed some of the first transplants for leukemia patients. Iomab-B is intended to be an induction and conditioning agent prior to a BMT for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55. BMT is the only potentially curative option for AML i.e. for this patient population that currently has a survival prognosis of 2-6 months which means that if Iomab-B is successful it would create a new market segment and offer patients a great clinical benefit and a hope for a cure. Actinium Pharmaceuticals licensed Iomab from the Hutch in 2012 and prior to us licensing Iomab, it had been studied in almost 300 patients in several phase 1 and phase 2 clinical trials in an array of blood cancers, both leukemias and lymphomas. Actinium is now the sponsor of a pivotal phase 3 trial for Iomab-B to study its use as an induction and conditioning agent prior to a bone marrow transplantation in patients with relapsed or refractory AML who are over the age of 55. This trial, which we have named the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial, started at the end of June 2016 and we expect to enroll 150 patients by the end of 2017. The primary endpoint of the SIERRA trial is durable complete remissions (dCR) of 6 months. The study arm will consist of Iomab-B administration followed by a  bone marrow transplantation, patients will be evaluated for dCR at 6 months after engraftment, which will be assessed at day 28 or day 56. The control arm of the study will be physician’s choice of chemotherapy and if the patient is able to achieve a complete remission (CR) they may receive a BMT or some other form of treatment with curative intent. The study is designed to evaluate if the study arm of Iomab-B and a BMT can double the dCR rate of the control arm, which is designed to replicate the current treatment regimen prior to a bone marrow transplantation .