понедельник, 18 апреля 2011 г.

News From The Journal Of Clinical Investigation: Nov. 8, 2010

ONCOLOGY: An Enigma for tumor suppression



One of the most well studied suppressors of tumor formation and development is the protein p53. A team of researchers, led by Dong-Soo Im, at the Korea Research Institute of Bioscience and Biotechnology, South Korea, has now provided new insight into how levels of this protein are regulated in human cell lines. Specifically, the team identified a mechanism by which the protein Enigma promotes p53 degradation. Among the several lines of evidence that this mechanism has a role in tumor development and progression was the observation that Enigma promoted human cancer cell line survival and resistance to chemotherapy by suppressing p53-induced cell death in a mouse xenograft model. The authors therefore suggest that Enigma could be new therapeutic target for selective activation of the tumor suppressor p53.



TITLE: Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice



DERMATOLOGY: Improving wound healing in diabetes



Individuals with diabetes are at increased risk of wounds not healing properly, and this leads to over 72,000 amputations each year. Impaired generation of new blood vessels at the wound site is a key factor behind poor wound healing in these patients. This in turn is in part because cells responsible for making new blood vessel-lining cells (endothelial progenitor cells) are functionally impaired. A team of researchers, led by Alex Chen, at the University of Pittsburgh School of Medicine, Pittsburgh, has now identified a reason why endothelial progenitor cells are defective in diabetic mice.



In the study, endothelial progenitor cells were found to express decreased levels of the protein manganese superoxide dismutase and this reduced their ability to contribute to new blood vessel generation, thereby impairing wound healing. Importantly, gene therapy to replace manganese superoxide dismutase in endothelial progenitor cells from diabetic mice improved their wound healing functionality. The authors therefore suggest that a similar gene therapy approach may be of benefit to patients with diabetes.



TITLE: Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice



MUSCLE BIOLOGY: A complement to muscle wasting



Individuals with mutations in their dysferlin gene develop one of a group of muscle-wasting diseases sometimes referred to as dysferlinopathies. The exact mechanism(s) underlying the muscle wasting in these individuals is not completely understood. Now, a team of researchers, led by Kevin Campbell, at The University of Iowa, Iowa City, has identified a role for a component of the immune system that is involved in promoting inflammation (specifically, the complement system) in the muscle disease experienced by mice that lack dysferlin and thereby model dysferlinopathies. Among the several lines of evidence generated to support this conclusion was the observation that genetic manipulation of dysferlin-deficient mice such that the lacked the central complement protein C3 ameliorated the muscle wasting observed in dysferlin-deficient mice. These data lead the authors to suggest that targeting the complement system might provide a way to treat dysferlinopathies.
















TITLE: Genetic ablation of complement C3 attenuates muscle pathology in dysferlin-deficient mice



PULMONARY BIOLOGY: Explaining a key aspect of an inherited lung disease



Some individuals inherit a defect in production of the protein alpha-1 antitrypsin (AAT). This causes a chronic lung disease that is characterized by excessive numbers of immune cells known as neutrophils in the lungs. A team of researchers, led by Emer Reeves, at the Royal College of Surgeons in Ireland, has now identified two mechanisms explaining why human neutrophils accumulate in the lungs of individuals with an AAT deficiency, something previously unknown. Of clinical interest, AAT augmentation therapy counteracted these mechanisms, providing insight into why it works to reduce the lung disease associated with AAT deficiency.



TITLE: alpha-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8



HEMATOLOGY: Rescuing red blood cell production after a bone marrow transplant



Bone marrow transplantation is used to treat some forms of cancer and some other diseases that affect blood cells. One complication after a bone marrow transplant is anemia, i.e., low levels of red blood cells. Robert Paulson and colleagues, at Pennsylvania State University, University Park, have now identified a pathway responsible for the production of new red blood cells shortly after bone marrow transplantation in mice. Specifically, they find that signaling initiated by the protein BMP4 promotes the development of red blood cell precursors in the spleen. These cells act to produce red blood cells in the immediate aftermath of bone marrow transplantation and function until the bone marrow transplant has taken hold and can take over the job of generating red blood cells. The authors point out that it might be possible to promote red blood cell production by targeting the BMP4 signaling pathway but that it will be necessary to determine whether or not this pathway functions in humans before its real clinical impact is known.



TITLE: Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors



Source:

Karen Honey


Journal of Clinical Investigation

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