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https://www.readbyqxmd.com/read/29228234/tgfbr2-inactivation-facilitates-cellular-plasticity-and-development-of-pten-null-prostate-cancer
#1
Wei Zhao, Peng Tan, Qingyuan Zhu, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y Wang, Rong-Fu Wang
Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo...
December 8, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29224900/single-fraction-stereotactic-ablative-body-radiotherapy-for-oligometastasis-outcomes-from-132-consecutive-patients
#2
S Gandhidasan, D Ball, T Kron, M Bressel, M Shaw, J Chu, S Chander, G Wheeler, N Plumridge, B Chesson, S David, S Siva
AIMS: Stereotactic ablative body radiotherapy (SABR) is currently used to treat oligometastases, but the optimum dose/fractionation schedule is unknown. In this study, we evaluated outcomes after single fraction SABR in patients with oligometastatic disease. MATERIALS AND METHODS: Single institutional retrospective review of patients treated with single fraction SABR for one to three oligometastases between 2010 and 2015. The primary outcome was freedom from widespread disease defined as distant recurrence not amenable to surgery or SABR; or recurrence with four or more metastases...
December 7, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29212906/osteoblasts-are-rapidly-ablated-by-virus-induced-systemic-inflammation-following-lymphocytic-choriomeningitis-virus-or-pneumonia-virus-of-mice-infection-in-mice
#3
Steven Maltby, Alyssa J Lochrin, Bianca Bartlett, Hock L Tay, Jessica Weaver, Ingrid J Poulton, Maximilian W Plank, Helene F Rosenberg, Natalie A Sims, Paul S Foster
A link between inflammatory disease and bone loss is now recognized. However, limited data exist on the impact of virus infection on bone loss and regeneration. Bone loss results from an imbalance in remodeling, the physiological process whereby the skeleton undergoes continual cycles of formation and resorption. The specific molecular and cellular mechanisms linking virus-induced inflammation to bone loss remain unclear. In the current study, we provide evidence that infection of mice with either lymphocytic choriomeningitis virus (LCMV) or pneumonia virus of mice (PVM) resulted in rapid and substantial loss of osteoblasts from the bone surface...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29208899/in-vivo-transplantation-of-3d-encapsulated-ovarian-constructs-in-rats-corrects-abnormalities-of-ovarian-failure
#4
Sivanandane Sittadjody, Justin M Saul, John P McQuilling, Sunyoung Joo, Thomas C Register, James J Yoo, Anthony Atala, Emmanuel C Opara
Safe clinical hormone replacement (HR) will likely become increasingly important in the growing populations of aged women and cancer patients undergoing treatments that ablate the ovaries. Cell-based HRT (cHRT) is an alternative approach that may allow certain physiological outcomes to be achieved with lower circulating hormone levels than pharmacological means due to participation of cells in the hypothalamus-pituitary-ovary feedback control loop. Here we describe the in vivo performance of 3D bioengineered ovarian constructs that recapitulate native cell-cell interactions between ovarian granulosa and theca cells as an approach to cHRT...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29204925/ultrasound-based-triggered-drug-delivery-to-tumors
#5
REVIEW
Ankit Jain, Ankita Tiwari, Amit Verma, Sanjay K Jain
Over the past few decades, applications of ultrasound (US) in drug delivery have been documented widely for local and site-specific release of bioactives in a controlled manner, after acceptable use in mild physical therapy for tendinitis and bursitis, and for high-energy applications in fibroid ablation, cataract removal, bone fracture healing, etc. US is a non-invasive, efficient, targetable and controllable technique. Drug delivery can be enhanced by applying directed US in terms of targeting and intracellular uptake...
December 4, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29204695/percutaneous-image-guided-ablation-in-the-treatment-of-osseous-metastases-from-non-small-cell-lung-cancer
#6
Yuntong Ma, Adam N Wallace, Saiama N Waqar, Daniel Morgensztern, Thomas P Madaelil, Anderanik Tomasian, Jack W Jennings
INTRODUCTION: Percutaneous image-guided ablation is an emerging minimally invasive therapy for patients with metastatic bone disease for whom radiation therapy is ineffective or contraindicated. The purpose of this study was to examine the safety and efficacy of percutaneous ablation in achieving pain palliation and local tumor control of osseous metastases from non-small cell lung cancer (NSCLC). METHODS: A retrospective review was performed of 76 musculoskeletal metastases in 45 patients treated with percutaneous ablation...
December 4, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/29203593/loss-of-p53-compensates-osteopenia-in-murine-mysm1-deficiency
#7
Melanie Haffner-Luntzer, Anna Kovtun, Verena Fischer, Katja Prystaz, Adelheid Hainzl, Carsten M Kroeger, Ioanna Krikki, Titus J Brinker, Anita Ignatius, Martina Gatzka
Histone modifications critically contribute to the epigenetic orchestration of bone homeostasis-in part, by modifying the access of transcription factors to specific genes involved in the osteogenic differentiation process of bone marrow mesenchymal stem cells (MSCs) and osteoblasts. Based on our previous finding that histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53 axis in hematopoiesis and tissue development, we analyzed the molecular basis of the skeletal phenotype of Mysm1-deficient mice and dissected the underlying p53-dependent and -independent mechanisms...
December 4, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29203432/propionibacterium-acnes-prosthetic-joint-infection-diagnosis-and-treatment
#8
REVIEW
P Boisrenoult
Propionibacterium acnes is a commensal skin bacterium, regularly implicated in prosthetic joint infection, particularly of the shoulder. Diagnosis has been improved by progress in bacteriological techniques: longer culture time, liquid medium culture, MALDI-TOF mass spectrography, and universal 16S rRNA PCR, associated by some authors to sonication of ablated implants. P. acnes pathogenicity involves many virulence factors, notably including biofilm formation. P. acnes may lead to infection that is clinically evident or, frequently, relatively asymptomatic...
December 1, 2017: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/29201060/osteogenic-differentiation-of-hdpscs-on-biogenic-bone-apatite-thin-films
#9
Michele Bianchi, Alessandra Pisciotta, Laura Bertoni, Matteo Berni, Alessandro Gambardella, Andrea Visani, Alessandro Russo, Anto de Pol, Gianluca Carnevale
A previous study reported the structural characterization of biogenic apatite (BAp) thin films realized by a pulsed electron deposition system by ablation of deproteinized bovine bone. Thin films annealed at 400°C exhibited composition and crystallinity degree very close to those of biogenic apatite; this affinity is crucial for obtaining faster osseointegration compared to conventional, thick hydroxyapatite (HA) coatings, for both orthopedics and dentistry. Here, we investigated the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells (hDPCS) on as-deposited and heat-treated BAp and stoichiometric HA...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29193144/simulating-thermal-effects-of-mr-guided-focused-ultrasound-in-cortical-bone-and-its-surrounding-tissue
#10
Thomas J Hudson, Thomas Looi, Samuel Pichardo, Joao Amaral, Michael Temple, James M Drake, Adam C Waspe
PURPOSE: Magnetic resonance guided focused ultrasound (MRgFUS) is emerging as a treatment alternative for osteoid osteoma and painful bone metastases. This study describes a new simulation platform that predicts the distribution of heat generated by MRgFUS when applied to bone tissue. METHODS: Calculation of the temperature distribution was performed using two mathematical models. The first determined the propagation and absorption of acoustic energy through each medium, and this was performed using a multi-layered approximation of the Rayleigh integral...
November 28, 2017: Medical Physics
https://www.readbyqxmd.com/read/29183785/ablation-of-gs%C3%AE-signaling-in-osteoclast-progenitor-cells-adversely-affects-skeletal-bone-maintenance
#11
REVIEW
Girish Ramaswamy, John Fong, Niambi Brewer, Hyunsoo Kim, Deyu Zhang, Yongwon Choi, Frederick S Kaplan, Eileen M Shore
Gsα, the alpha stimulatory subunit of heterotrimeric G proteins that activates downstream signaling through the adenylyl cyclase and cAMP/PKA pathway, plays an important role in bone development and remodeling. The role of Gsα in mesenchymal stem cell (MSC) differentiation to osteoblasts has been demonstrated in several mouse models of Gsα inactivation. Previously, using mice with heterozygous germline deletion of Gsα (Gnas+/p-), we identified a novel additional role for Gsα in bone remodeling, and showed the importance of Gnas in maintaining bone quality by regulating osteoclast differentiation and function...
November 25, 2017: Bone
https://www.readbyqxmd.com/read/29176619/stim1-promotes-migration-phagosomal-maturation-and-antigen-cross-presentation-in-dendritic-cells
#12
Paula Nunes-Hasler, Sophia Maschalidi, Carla Lippens, Cyril Castelbou, Samuel Bouvet, Daniele Guido, Flavien Bermont, Esen Y Bassoy, Nicolas Page, Doron Merkler, Stéphanie Hugues, Denis Martinvalet, Bénédicte Manoury, Nicolas Demaurex
Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell activation to promote immunity to intracellular pathogens, viruses and cancer. Phagocytosed antigens generate potent T cell responses, but the signalling and trafficking pathways regulating their cross-presentation are unclear. Here, we show that ablation of the store-operated-Ca2+-entry regulator STIM1 in mouse myeloid cells impairs cross-presentation and DC migration in vivo and in vitro. Stim1 ablation reduces Ca2+ signals, cross-presentation, and chemotaxis in mouse bone-marrow-derived DCs without altering cell differentiation, maturation or phagocytic capacity...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29168402/liquid-metal-bath-as-conformable-soft-electrodes-for-target-tissue-ablation-in-radio-frequency-ablation-therapy
#13
Xuyang Sun, Zhi-Zhu He, Zhong-Shan Deng, Yi-Xin Zhou, Jing Liu
BACKGROUND: Radio-frequency ablation has been an important physical method for tumor hyperthermia therapy. The conventional rigid electrode boards are often uncomfortable and inconvenient for performing surgery on irregular tumors, especially for those tumors near the joints, such as ankles, knee-joints or other facets like finger joints. MATERIAL AND METHODS: We proposed and demonstrated a highly conformable tumor ablation strategy through introducing liquid metal bath as conformable soft electrodes...
November 23, 2017: Minimally Invasive Therapy & Allied Technologies: MITAT
https://www.readbyqxmd.com/read/29167177/smoothened-signaling-in-the-mouse-osteoblastoid-lineage-is-required-for-efficient-b-lymphopoiesis
#14
Wenyan Lu, Dominic Dordai, David Huso, Stephen Desiderio
The stromal signals that promote B lymphopoiesis remain poorly understood. Hedgehog (Hh) signaling promotes B lymphopoiesis in a non-cell autonomous fashion in vitro and depletion of the Hh effector smoothened (Smo) from stromal cells is associated with the loss of osteoblastoid markers. These observations suggested that Hh signaling in the osteoblastoid lineage promotes B lymphopoiesis in vivo. To test this we developed a mouse model for conditional ablation of Smo in the osteoblastoid lineage. Depletion of Smo from osteoblastoid cells is associated with profound and selective reductions in the number and proportion of bone marrow B lymphoid progenitors...
November 22, 2017: Blood
https://www.readbyqxmd.com/read/29165823/identification-of-predisposing-factors-for-osteonecrosis-of-the-jaw-after-marginal-mandibulectomy-in-the-surgical-management-of-oral-squamous-cell-carcinoma
#15
Ran Ito, Jung-Ju Huang, Wei-Chuan Hsieh, Huang-Kai Kao, William Wei-Kai Lao, Ku-Hao Fang, Yenlin Huang, Yu-Liang Chang, Ming-Huei Cheng, Kai-Ping Chang
BACKGROUND: The aim of this study is to evaluate osteonecrosis of the jaw (ONJ) with the extent of marginal mandibulectomy. METHODS: Between January 2006 and December 2012, 3087 patients undergoing ablative resection were consecutively enrolled. Among them, 345 cases undergoing marginal mandibulectomy were retrospectively reviewed. RESULTS: The occurrence of ONJ was 5.51% and associated with body mass index, overall stage, diabetes, concomitant mandibulotomy, and radiotherapy (P = 0...
November 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29162538/metformin-promotes-the-proliferation-and-differentiation-of-murine-preosteoblast-by-regulating-the-expression-of-sirt6-and-oct4
#16
Wei Mu, Zhuoran Wang, Chuanyu Ma, Yunyun Jiang, Nannan Zhang, Kaiqiang Hu, Liyuan Li, Zhao Wang
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29160182/enhanced-bone-regeneration-via-diabetic-cell-based-adenoviral-bmp2-gene-therapy-in-diabetic-animals
#17
Shin-Young Park, Kyoung-Hwa Kim, Chan Ho Park, Seung-Yun Shin, In-Chul Rhuy, Yong-Moo Lee, Yang Jo Seol
The application of bone morphogenetic protein 2 (BMP-2) has been extensively investigated to improve diabetes-impaired bone healing; however, the delivery of BMP-2 via gene therapy for bone regeneration has rarely been investigated in diabetic animals. In this study, we aimed to evaluate which cells induce more new bone formation in diabetic animals when cell-based BMP2 gene therapy is applied. For this purpose, we harvested bone marrow stromal cells (BMSCs) twice in the same animal before (non-diabetic BMSCs; nBMSCs) and after diabetes induction (diabetic BMSCs; dBMSCs) using modified bone marrow ablation methods...
November 21, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29155425/granulocyte-derived-tnf%C3%AE-promotes-vascular-and-hematopoietic-regeneration-in-the-bone-marrow
#18
Emily Bowers, Anastasiya Slaughter, Paul S Frenette, Rork Kuick, Oscar M Pello, Daniel Lucas
Endothelial cells are a critical component of the bone marrow (BM) stromal network, which maintains and regulates hematopoietic cells. Vascular regeneration precedes, and is necessary for, successful hematopoietic stem cell (HSC) transplantation, the only cure for most hematopoietic diseases. Recent data suggest that mature hematopoietic cells regulate BM stromal-cell function. Whether a similar cross-talk regulates the BM vasculature is not known. Here we found that donor hematopoietic cells act on sinusoidal endothelial cells and induce host blood vessel and hematopoietic regeneration after BM transplantation in mice...
November 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29149593/notch2-hajdu-cheney-mutations-escape-scf-fbw7-dependent-proteolysis-to-promote-osteoporosis
#19
Hidefumi Fukushima, Kouhei Shimizu, Asami Watahiki, Seira Hoshikawa, Tomoki Kosho, Daiju Oba, Seiji Sakano, Makiko Arakaki, Aya Yamada, Katsuyuki Nagashima, Koji Okabe, Satoshi Fukumoto, Eijiro Jimi, Anna Bigas, Keiichi I Nakayama, Keiko Nakayama, Yoko Aoki, Wenyi Wei, Hiroyuki Inuzuka
Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149200/heterozygous-deletion-of-both-sclerostin-sost-and-connexin43-gja1-genes-in-mice-is-not-sufficient-to-impair-cortical-bone-modeling
#20
Susan K Grimston, Francesca Fontana, Marcus Watkins, Roberto Civitelli
Connexin43 (Cx43) is the main gap junction protein expressed in bone forming cells, where it modulates peak bone mass acquisition and cortical modeling. Genetic ablation of the Cx43 gene (Gja1) results in cortical expansion with accentuated periosteal bone formation associated with decreased expression of the Wnt inhibitor sclerostin. To determine whether sclerostin (Sost) down-regulation might contribute to periosteal expansion in Gja1 deficient bones, we took a gene interaction approach and crossed mice harboring germline null alleles for Gja1 or Sost to generate single Gja1+/-and Sost+/-and double Gja1+/-;Sost+/-heterozygous mice...
2017: PloS One
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