British Dental Journal 221, 746 (2016). doi:10.1038/sj.bdj.2016.934
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Παρασκευή 16 Δεκεμβρίου 2016
Complement-mediated inflammation and injury in brain dead organ donors
Source:Molecular Immunology
Author(s): Felix Poppelaars, Marc A. Seelen
The importance of the complement system in renal ischemia-reperfusion injury and acute rejection is widely recognized, however its contribution to the pathogenesis of tissue damage in the donor remains underexposed. Brain-dead (BD) organ donors are still the primary source of organs for transplantation. Brain death is characterized by hemodynamic changes, hormonal dysregulation, and immunological activation. Recently, the complement system has been shown to be involved. In BD organ donors, complement is activated systemically and locally and is an important mediator of inflammation and graft injury. Furthermore, complement activation can be used as a clinical marker for the prediction of graft function after transplantation. Experimental models of BD have shown that inhibition of the complement cascade is a successful method to reduce inflammation and injury of donor grafts, thereby improving graft function and survival after transplantation. Consequently, complement-targeted therapeutics in BD organ donors form a new opportunity to improve organ quality for transplantation. Future studies should further elucidate the mechanism responsible for complement activation in BD organ donors.
http://ift.tt/2hXiSgi
Effective Interprofessional Perioperative Training Requires not Only Multi-Professional and Multi-Department, but also Multi-Hospital Participation
Publication date: Available online 15 December 2016
Source:Journal of Surgical Education
Author(s): Nobuyasu Komasawa, Benjamin W. Berg, Toshiaki Minami
http://ift.tt/2gSQsID
How Knowledge Relates to Confidence in Orthopedics and Emergency Medicine Regarding Return to Sport and Rehabilitation in Foot and Ankle Trauma
Publication date: Available online 16 December 2016
Source:Journal of Surgical Education
Author(s): Sarah Johnson-Lynn, David Townshend
ObjectiveThe aim of this study was to survey the knowledge of registrars in emergency medicine and orthopedics on 5 common injuries to the foot and ankle and compare this knowledge, and self-reported confidence in giving it, with that of consultants and physiotherapists of various levels of experience.DesignAn online survey was used to gather the information using scenario-based open and closed questions.ParticipantsA total of 102 health care professionals, who regularly deal with sports injuries, were recruited. These included consultant orthopedic surgeons with a subspecialty interest in foot and ankle surgery, orthopedic surgeons in other specialties, extended scope physiotherapy practitioners (ESPs) in foot and ankle and general musculoskeletal practice, emergency medicine consultants, emergency medicine registrars, orthopedic registrars, senior physiotherapists, and junior physiotherapists.SettingThe participants were drawn from various health care institutions in the North East of England.ResultsConsultant foot and ankle surgeons and extended scope practitioners in foot and ankle both scored significantly on knowledge of rehabilitation program design than either set of registrars. For 2 of the case scenarios, there was a significant difference in scores between either orthopedic consultants or ESPs and registrars (p < 0.05). For total score, there was a trend for extended scope practitioners to score higher than both sets of registrars, but this did not reach significance.Correlation coefficients for knowledge and self-reported confidence ranged between 0.009 and 0.33, demonstrating only weak positive linear correlation between scenario score and reported confidence in advice given.ConclusionsThe most significant area of gaps in knowledge among the 2 groups of registrars was in the specifics of rehabilitation programs. There was markedly higher confidence with greater seniority. Registrars in emergency medicine and orthopedics are likely to benefit from case-based teaching in sports injury rehabilitation.
http://ift.tt/2h9cQcw
Molecular Checkpoint Decisions Made by Subverted Vascular Niche Transform Indolent Tumor Cells into Chemoresistant Cancer Stem Cells
Publication date: Available online 15 December 2016
Source:Cancer Cell
Author(s): Zhongwei Cao, Joseph M. Scandura, Giorgio G. Inghirami, Koji Shido, Bi-Sen Ding, Shahin Rafii
Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R). However, chemotherapy triggers TECs to suppress IGFBP7, and this stimulates IGF1R+ TSCs to express FGF4, inducing a feedforward FGFR1-ETS2 angiocrine cascade that obviates TEC IGFBP7. Thus, loss of IGFBP7 and upregulation of IGF1 activates the FGF4-FGFR1-ETS2 pathway in TECs and converts naive tumor cells to chemoresistant TSCs, thereby facilitating their invasiveness and progression.
Graphical abstract
Teaser
Cao et al. show that IGFBP7 expressed by tumor-associated endothelial cells (TECs) suppresses IGF1R signaling and the stem cell-like property of tumor cells. Tumor-derived FGF4 activates an FGFR1-ETS2 axis in TECs that upregulates IGF1 and downregulates IGFBP7, facilitating IGF1R+ tumor stem-like cell expansion.http://ift.tt/2hDwr5M
Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling
Publication date: Available online 15 December 2016
Source:Cancer Cell
Author(s): Yoku Hayakawa, Kosuke Sakitani, Mitsuru Konishi, Samuel Asfaha, Ryota Niikura, Hiroyuki Tomita, Bernhard W. Renz, Yagnesh Tailor, Marina Macchini, Moritz Middelhoff, Zhengyu Jiang, Takayuki Tanaka, Zinaida A. Dubeykovskaya, Woosook Kim, Xiaowei Chen, Aleksandra M. Urbanska, Karan Nagar, Christoph B. Westphalen, Michael Quante, Chyuan-Sheng Lin, Michael D. Gershon, Akira Hara, Chun-Mei Zhao, Duan Chen, Daniel L. Worthley, Kazuhiko Koike, Timothy C. Wang
Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1+ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1+ cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in an ACh muscarinic receptor-3 (M3R)-dependent manner, in part through suppression of yes-associated protein (YAP) function. This feedforward ACh-NGF axis activates the gastric cancer niche and offers a compelling target for tumor treatment and prevention.
Graphical abstract
Teaser
Hayakawa et al. use a series of mouse models to show that acetylcholine from Dclk1+ tuft cells and nerves induces NGF in gastric epithelial cells, which promotes neuron expansion and tumorigenesis. YAP is activated through the cholinergic signaling, and inhibition of this pathway can block NGF-driven tumors.http://ift.tt/2hDxnHi
Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer
Abstract
Background
In spite of various treatment options currently available, ovarian cancer (OC) still remains a leading cause of death in women world-wide. Diagnosis at an early stage is one of the most important factors that determines survival. Current clinical diagnostic tools have, however, a limited efficacy in early OC detection. Therefore, there is a critical need for new (early) diagnostic biomarkers and tools. Through advances in genomic, proteomic and metabolomic techniques, several novel molecular OC biomarkers have recently been identified. These biomarkers are currently subject to validation. In addition, integration of genomic, proteomic and metabolomic data, in conjunction with epidemiologic and clinical data, is considered essential for obtaining useful results. Interesting recent work has already shown that specific diagnostic biomarkers, such as BRCA mutations, may have profound therapeutic implications. Here, we review the current state of OC research through literature and database searches, with a focus on various recently identified biomarkers via different technologies for the (early) diagnosis, prognosis and treatment of OC.
Conclusions
Multi-biomarker panels accompanied by a meticulous determination of their sensitivity and specificity, as well their validation, using multivariate analyses will be critical for its clinical application, including early OC detection and tailor-made OC treatment.
http://ift.tt/2hFZmFT
Endocytosis, Metastasis and Beyond: Multiple Facets of SNX9
Source:Trends in Cell Biology
Author(s): Nawal Bendris, Sandra L. Schmid
Sorting nexin (SNX)9 was first discovered as an endocytic accessory protein involved in clathrin-mediated endocytosis. However, recent data suggest that SNX9 is a multifunctional scaffold that coordinates membrane trafficking and remodeling with changes in actin dynamics to affect diverse cellular processes. Here, we review the accumulated knowledge on SNX9 with an emphasis on its recently identified roles in clathrin-independent endocytic pathways, cell invasion, and cell division, which have implications for SNX9 function in human disease, including cancer.
http://ift.tt/2hOQpxl
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