The outlook for patients with breast cancer is determined in part by whether or not their tumor has spread to other sites in the body. A team of researchers, led by Roman Perez-Fernandez and colleagues, at the University of Santiago de Compostela, Spain, has now identified in a subset of patients with breast cancer, a marker associated with the occurrence of tumors at distant sites; a finding that they hope might help predict a patient's outlook more accurately. Specifically, the team found that in patients with breast cancer that was accompanied by the presence of tumor cells in nearby lymph nodes, high levels of expression of the protein Pit-1 were associated with tumor spread to distant sites. The authors therefore suggest that analysis of Pit-1 expression in human breast tumor samples could help predict the outlook for patients with lymph node–positive breast cancer.
TITLE: Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis
AUTHOR CONTACT:
Roman Perez-Fernandez
University of Santiago de Compostela, Santiago de Compostela, Spain.
Phone: 34.8818.12257; Fax: 34.981.574145; E-mail: roman.perez.fernandez@usc.es.
View this article at: http://www.jci.org/articles/view/42015?key=b82dbe71403c8d490e53
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
AUTHOR CONTACT:
Dong-Soo Im
Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Phone: 82.42.860.4172; Fax: 82.42.860.4597; E-mail: imdongsu@kribb.re.kr.
View this article at: http://www.jci.org/articles/view/42674?key=efd09435f3d59063fb1c
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
AUTHOR CONTACT:
Alex F. Chen
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Phone: 412.624.6769; Fax: 412.648.7107; E-mail: chena5@upmc.edu.
View this article at: http://www.jci.org/articles/view/36858?key=a299074908118e6d4901
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
AUTHOR CONTACT:
Kevin P. Campbel
Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Phone: 319.335.7867; Fax: 319.335.6957; E-mail: Kevin-campbell@uiowa.edu.
View this article at: http://www.jci.org/articles/view/42390?key=1aea8d028bb4436c8ab1
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
AUTHOR CONTACT:
Emer P. Reeves
Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Phone: 353.1.8093877; Fax: 353.1.8093808; Email: emerreeves@rcsi.ie.
View this article at: http://www.jci.org/articles/view/41196?key=aa6adc1ee1b4975f1356
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
AUTHOR CONTACT:
Robert F. Paulson
Pennsylvania State University, University Park, Pennsylvania, USA.
Phone: 814.863.6306; Fax: 814.863.6140; E-mail: rfp5@psu.edu.
View this article at: http://www.jci.org/articles/view/41291?key=2756ef91cfa2b2e8f486
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