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https://www.readbyqxmd.com/read/28057913/humoral-hypercalcemia-in-uterine-cancers-a-case-report-and-literature-review
#1
Vijeyaluxmy Motilal Nehru, Gwenalyn Garcia, Juan Ding, Fanyi Kong, Qun Dai
BACKGROUND Paraneoplastic hypercalcemia is a well-described complication associated with a variety of malignancies. However, its incidence in gynecological malignancies is low. CASE REPORT A 53-year-old woman presented with progressive abdominal distention and irregular vaginal bleeding of several weeks' duration. A contrast CT abdomen and pelvis was significant for a mass in the lower uterine/cervical region, multiple peritoneal and omental masses, enlarged pelvic and paraaortic lymph nodes, and large-volume ascites...
January 6, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28043938/mtorc1-activation-downregulates-fgfr3-and-pth-pthrp-receptor-in-articular-chondrocytes-to-initiate-osteoarthritis
#2
H Zhang, H Wang, C Zeng, B Yan, J Ouyang, X Liu, Q Sun, C Zhao, H Fang, J Pan, D Xie, J Yang, T Zhang, X Bai, D Cai
OBJECTIVE: Articular chondrocyte activation, involving aberrant proliferation and prehypertrophic differentiation, is essential for osteoarthritis (OA) initiation and progression. Disruption of mechanistic target of rapamycin complex 1 (mTORC1) promotes chondrocyte autophagy and survival, and decreases the severity of experimental OA. However, the role of cartilage mTORC1 activation in OA initiation is unknown. In this study, we elucidated the specific role of mTORC1 activation in OA initiation, and identify the underlying mechanisms...
December 31, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28030842/loss-of-runx3-expression-inhibits-bone-invasion-of-oral-squamous-cell-carcinoma
#3
Junhee Park, Hyun-Jeong Kim, Ki Rim Kim, Sun Kyoung Lee, Hyungkeun Kim, Kwang-Kyun Park, Won-Yoon Chung
High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027321/elevated-fibroblast-growth-factor-signaling-is-critical-for-the-pathogenesis-of-the-dwarfism-in-evc2-limbin-mutant-mice
#4
Honghao Zhang, Nobuhiro Kamiya, Takehito Tsuji, Haruko Takeda, Greg Scott, Sudha Rajderkar, Manas K Ray, Yoshiyuki Mochida, Benjamin Allen, Veronique Lefebvre, Irene H Hung, David M Ornitz, Tetsuo Kunieda, Yuji Mishina
Ellis-van Creveld (EvC) syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN). While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC patients, and in particular why limb development is affected, but not other aspects of organogenesis that also require Hedgehog signaling...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27994624/regulatory-mechanisms-of-the-ihh-pthrp-signaling-pathway-in-fibrochondrocytes-in-entheses-of-pig-achilles-tendon
#5
Xuesong Han, Yanfeng Zhuang, Zhihong Zhang, Lin Guo, Wanming Wang
This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27920805/abaloparatide
#6
REVIEW
Stefano Gonnelli, Carla Caffarelli
Abaloparatide is an investigational analog of human PTHrP (1-34) being developed for the treatment of osteoporosis. The amino-acid sequence of abaloparatide is identical to that of PTHrP in the first 20 amino-acids, while over half of the remaining amino-acids are different. Some studies in animals and in humans reported that abaloparatide presented a potent anabolic activity with reduced effects on bone resorption as compared to that observed with teriparatide. This may be due to a more transient signaling response of abaloparatide related to differing affinities of the two drugs to the specific conformations of the PTH1 receptor...
May 2016: Clinical Cases in Mineral and Bone Metabolism
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
#7
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
#8
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
#9
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
#10
T John Martin, Ego Seeman
No abstract text is available yet for this article.
January 2017: 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
#11
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
#12
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
#13
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
#14
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
#15
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...
January 2017: 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
#16
REVIEW
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
#17
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
#18
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
#19
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
#20
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
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