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PTHrP

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https://www.readbyqxmd.com/read/27904108/denosumab-is-effective-for-controlling-serum-calcium-levels-in-patients-with-humoral-hypercalcemia-of-malignancy-syndrome-a-case-report-on-parathyroid-hormone-related-protein-producing-cholangiocarcinoma
#1
Norihiro Ashihara, Koji Nakajima, Yoshiyuki Nakamura, Mutsuhiro Kobayashi, Kumiko Shirahata, Chika Maeda, Takeshi Uehara, Daisuke Gomi, Nobuo Ito
Hypercalcemia resulting in the elevation of serum parathyroid hormone-related protein (PTHrP) and suppression of serum PTH was observed in a patient with advanced cholangiocarcinoma (CCC) and multiple lymph node metastases. We confirmed humoral hypercalcemia of malignancy based on PTHrP-producing CCC. Chemotherapy with gemcitabine and cisplatin could not control the patient's serum PTHrP levels and the patient was affected with bisphosphonate-refractory hypercalcemia. We administered a single dose of denosumab, an anti-receptor activator of nuclear factor-kappaB ligand monoclonal antibody, and the patient's serum calcium levels remained close to the normal range for approximately 3 weeks without additional treatment...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27895794/trousseau-s-syndrome-caused-by-bladder-cancer-producing-granulocyte-colony-stimulating-factor-and-parathyroid-hormone-related-protein-a-case-report
#2
Tomonori Kato, Kenji Yasuda, Hiroaki Iida, Akihiko Watanabe, Yasuyoshi Fujiuchi, Shigeharu Miwa, Johji Imura, Akira Komiya
The present study reports a rare case of bladder cancer that caused Trousseau's syndrome, a malignancy-associated hypercoagulative state leading to venous or arterial thrombosis. A 38-year-old Japanese female patient experienced a sudden onset of visual field defects and lower limb weakness. Cerebral magnetic resonance imaging revealed multi-regional hypointense areas compatible with acute cerebral infarction. Despite the repeated administration of anticoagulant treatment with heparin, the condition could not be adequately controlled and thromboembolic events occasionally recurred...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27879134/on-a-mathematical-model-of-bone-marrow-metastatic-niche
#3
Ana Isabel Munoz, J Ignacio Tello
We propose a mathematical model to describe tumor cells movement towards a metastasis location into the bone marrow considering the influence of chemotaxis inhibition due to the action of a drug. The model considers the evolution of the signaling molecules CXCL-12 secreted by osteoblasts (bone cells responsible of the mineralization of the bone) and PTHrP (secreted by tumor cells) which activates osteoblast growth. The model consists of a coupled system of second order PDEs describing the evolution of CXCL-12 and PTHrP, an ODE of logistic type to model the Osteoblasts density and an extra equation for each cancer cell...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27859635/abaloparatide-is-an-anabolic-but-does-it-spare-resorption
#4
T J Martin, E Seeman
Abaloparatide is a novel peptide that shares aminoterminal sequence with PTHrP. It has been shown in a clinical trial to reduce vertebral and nonvertebral fracture risk and to promote bone formation in the aged osteopenic rat. It is proposed to produce its anabolic effect with less promotion of resorption than with teriparatide. This article is protected by copyright. All rights reserved.
November 18, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27848974/differential-expression-of-tgf-%C3%AE-superfamily-members-and-role-of-smad1-5-9-signalling-in-chondral-versus-endochondral-chondrocyte-differentiation
#5
Verena Dexheimer, Jessica Gabler, Katharina Bomans, Tanja Sims, Georg Omlor, Wiltrud Richter
Proteins of the transforming-growth-factor-β (TGF-β)-superfamily have a remarkable ability to induce cartilage and bone and the crosstalk of TGF-β - and BMP-signalling pathways appears crucial during chondrocyte development. Aim was to assess the regulation of TGF-β-superfamily members and of Smad2/3- and Smad1/5/9-signalling during endochondral in vitro chondrogenesis of mesenchymal stromal cells (MSC) relative to chondral redifferentiation of articular chondrocytes (AC) to adjust chondrocyte development of MSC towards a less hypertrophic phenotype...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27830194/effect-of-high-fat-diet-on-pulmonary-expression-of-parathyroid-hormone-related-protein-and-its-downstream-targets
#6
Learta Oruqaj, Svenja Forst, Rolf Schreckenberg, Javier Inserte, Marcos Poncelas, Jordi Bañeras, David Garcia-Dorado, Susanne Rohrbach, Klaus-Dieter Schlüter
AIMS: Parathyroid hormone-related protein (PTHrP) is involved in lung development and surfactant production. The latter one requires a paracrine interaction between type II alveolar cells and lipofibroblasts in which leptin triggers PTHrP-induced effects. Whether increased plasma leptin levels, as they occur in high fat diet, modify the expression of PTHrP remains unclear. Furthermore, the effect of high fat diet under conditions of forced pulmonary remodelling such as response to post myocardial infarction remains to be defined...
October 2016: Heliyon
https://www.readbyqxmd.com/read/27813116/distinct-osteomimetic-response-of-androgen-dependent-and-independent-human-prostate-cancer-cells-to-mechanical-action-of-fluid-flow-prometastatic-implications
#7
Álvaro González, Cira García de Durango, Verónica Alonso, Beatriz Bravo, Arancha Rodríguez de Gortázar, Alan Wells, Jerónimo Forteza, Fernando Vidal-Vanaclocha
BACKGROUND AND METHODS: Prostate cancer frequently expresses an osteomimetic phenotype, but it is unclear how it is regulated and what biological and clinical implications it confers. Because mechanical forces physiologically regulate bone-remodeling activity in osteocytes, we hypothesized that mechanical action of fluid flow (MAFF) at the cancer microenvironment may similarly foster prostate cancer cell osteomimicry. RESULTS: We showed that in vitro MAFF on androgen-dependent (LNCap) and androgen-independent (PC3) prostate cancer cells remarkably increased OPG, VEGF, RunX2, PTH1R, and PTHrP gene expression in both cell lines irrespective of their androgen dependency...
November 3, 2016: Prostate
https://www.readbyqxmd.com/read/27783097/breast-cancer-cells-and-bone-marrow-mesenchymal-stromal-cells-a-regulated-modulation-of-the-breast-tumor-in-the-context-of-immune-response
#8
Mehdi Najar, Hussein Fayyad-Kazan, Wissam H Faour, Bassam Badran, Fabrice Journe, Laurence Lagneaux
OBJECTIVE: The role of direct cell-cell interactions mediating selective bone metastasis by breast cancer cells (BCCs) niche is still mostly unknown. MATERIALS AND METHODS: Conditioned medium and direct cell-cell contacts experiments were used to investigate the effect of bone marrow-derived mesenchymal stromal cells (MSCs), osteoprogenitor-like cells (MG-63) and osteosarcoma cells (SaOS-2) on luminal-like (MCF-7) and basal-like (MDA-MB-231) BCCs flow cytometry was used to assess the purity of isolated BCCs and osteoblasts...
October 25, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27748532/one-year-of-abaloparatide-a-selective-activator-of-the-pth1-receptor-increased-bone-formation-and-bone-mass-in-osteopenic-ovariectomized-rats-without-increasing-bone-resorption
#9
Aurore Varela, Luc Chouinard, Elisabeth Lesage, Susan Y Smith, Gary Hattersley
Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss...
October 17, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27746743/calcium-sensing-receptor-in-breast-physiology-and-cancer
#10
Wonnam Kim, John J Wysolmerski
The calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coordinate calcium usage with calcium availability during milk production...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27743449/fracture-healing-physiology-and-the-quest-for-therapies-for-delayed-healing-and-nonunion
#11
Paul Kostenuik, Faisal M Mirza
Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses...
October 15, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27740628/hedgehog-signaling-in-bone-regulates-whole-body-energy-metabolism-through-a-bone-adipose-endocrine-relay-mediated-by-pthrp-and-adiponectin
#12
Xu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27738322/antagonizing-mir-218-5p-attenuates-wnt-signaling-and-reduces-metastatic-bone-disease-of-triple-negative-breast-cancer-cells
#13
Hanna Taipaleenmäki, Nicholas H Farina, Andre J van Wijnen, Janet L Stein, Eric Hesse, Gary S Stein, Jane B Lian
Wnt signaling is implicated in bone formation and activated in breast cancer cells promoting primary and metastatic tumor growth. A compelling question is whether osteogenic miRNAs that increase Wnt activity for bone formation are aberrantly expressed in breast tumor cells to support metastatic bone disease. Here we report that miR-218-5p is highly expressed in bone metastases from breast cancer patients, but is not detected in normal mammary epithelial cells. Furthermore, inhibition of miR-218-5p impaired the growth of bone metastatic MDA-MB-231 cells in the bone microenvironment in vivo...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27738315/hedgehog-and-tgf%C3%AE-signaling-converge-on-gli2-to-control-bony-invasion-and-bone-destruction-in-oral-squamous-cell-carcinoma
#14
Shellese A Cannonier, Cara B Gonzales, Kim Ely, Scott A Guelcher, Julie A Sterling
Oral Squamous Cell Carcinoma (OSCC) is the sixth most common cancer worldwide. OSCC invasion into the lymph nodes and mandible correlates with increased rates of recurrence and lower overall survival. Tumors that infiltrate mandibular bone proliferate rapidly and induce bone destruction. While survival rates have increased 12% over the last 20 years, this improvement is attributed to general advances in prevention, earlier detection, and updated treatments. Additionally, despite decades of research, the molecular mechanisms of OSCC invasion into the mandible are not well understood...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27731505/osteogenic-differentiation-of-periosteal-cells-during-fracture-healing
#15
REVIEW
Tao Wang, Xinping Zhang, Daniel D Bikle
Five to ten percent of fractures fail to heal normally leading to additional surgery, morbidity, and altered quality of life. Fracture healing involves the coordinated action of stem cells primarily coming from the periosteum which differentiate into the chondrocytes and osteoblasts, forming first the soft (cartilage) callus followed by the hard (bone) callus. These stem cells are accompanied by a vascular invasion that appears critical for the differentiation process and which may enable the entry of osteoclasts necessary for the remodeling of the callus into mature bone...
October 12, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27683064/pthrp-derived-peptides-restore-bone-mass-and-strength-in-diabetic-mice-additive-effect-of-mechanical-loading
#16
Marta Maycas, Kevin A McAndrews, Amy Y Sato, Gretel G Pellegrini, Drew M Brown, Matthew R Allen, Lilian I Plotkin, Arancha R Gortazar, Pedro Esbrit, Teresita Bellido
There is an unmet need to understand the mechanisms underlying skeletal deterioration in diabetes mellitus (DM) and to develop therapeutic approaches to treat bone fragility in diabetic patients. We demonstrate herein that mice with type 1 DM induced by streptozotocin exhibited low bone mass, inferior mechanical and material properties, increased bone resorption, decreased bone formation, increased apoptosis of osteocytes, and increased expression of the osteocyte-derived bone formation inhibitor Sost/sclerostin...
September 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27681305/braf-v600e-expression-correlates-with-ameloblastoma-aggressiveness
#17
Eduardo Rodrigues Fregnani, Danyel Elias da Cruz Perez, Oslei Paes de Almeida, Felipe Paiva Fonseca, Fernando Augusto Soares, Gilberto de Castro Junior, Fábio Abreu de Alves
AIMS: The aim of this study was to investigate whether the expression of BRAF-V600E determines an aggressive clinical and molecular presentation of ameloblastoma. METHODS AND RESULTS: Ninety-three cases of solid ameloblastomas were arranged in a 1.0-mm tissue microarray block. Immunohistochemistry against a large panel of cytokeratins (CK), epidermal growth factor receptor (EGFR), parathyroid hormone-related peptide (PTHrP), syndecan-1, Ki67, p53, and BRAF-V600E were done...
September 28, 2016: Histopathology
https://www.readbyqxmd.com/read/27666725/absence-of-collagen-ix-accelerates-hypertrophic-differentiation-in-the-embryonic-mouse-spine-through-a-disturbance-of-the-ihh-pthrp-feedback-loop
#18
Matthias Kamper, Mats Paulsson, Frank Zaucke
Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX ɑ2- and ɑ3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX -/- mice...
September 25, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27612440/advanced-quantitative-imaging-and-biomechanical-analyses-of-periosteal-fibers-in-accelerated-bone-growth
#19
Rajeev Chaudhary, Ming-Song Lee, Kuwabo Mubyana, Sarah Duenwald-Kuehl, Lyndsey Johnson, Jarred Kaiser, Ray Vanderby, Kevin W Eliceiri, David T Corr, Matthew S Chin, Wan-Ju Li, Paul J Campagnola, Matthew A Halanski
PURPOSE: The accepted mechanism explaining the accelerated growth following periosteal resection is that the periosteum serves as a mechanical restraint to restrict physeal growth. To test the veracity of this mechanism we first utilized Second Harmonic Generation (SHG) imaging to measure differences of periosteal fiber alignment at various strains. Additionally, we measured changes in periosteal growth factor transcription. Next we utilized SHG imaging to assess the alignment of the periosteal fibers on the bone both before and after periosteal resection...
November 2016: Bone
https://www.readbyqxmd.com/read/27605110/the-effect-of-mechanical-stretch-stress-on-the-differentiation-and-apoptosis-of-human-growth-plate-chondrocytes
#20
Keming Sun, Fangna Liu, Junjian Wang, Zhanhao Guo, Zejuan Ji, Manye Yao
The study is aimed to investigate the effect of stretch stress with different intensities on the differentiation and apoptosis of human plate chondrocytes. In the present study, the human epiphyseal plate chondrocytes were isolated and cultured in vitro. Toluidine blue staining and type II collagen immunohistochemical staining were used to identify the chondrocytes. Mechanical stretch stresses with different intensities were applied to intervene cells at 0-, 2000-, and 4000-μ strain for 6 h via a four-point bending system...
September 7, 2016: In Vitro Cellular & Developmental Biology. Animal
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