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PTHrP

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https://www.readbyqxmd.com/read/28323910/progressive-development-of-pth-resistance-in-patients-with-inactivating-mutations-on-the-maternal-allele-of-gnas
#1
Alessia Usardi, Asmaa Mamoune, Elodie Nattes, Jean-Claude Carel, Anya Rothenbuhler, Agnès Linglart
Background: PTH resistance is characterized by hypocalcaemia, hyperphosphatemia and elevated PTH in absence of vitamin D deficiency. Pseudohypoparathyroidism (PHP) type 1A (or iPPSD2, inactivating Signaling PTH/PTHrp Disorder 2 according to the new classification) is caused by mutations in the maternal GNAS allele. Objective: To assess PTH resistance over time in 20 patients affected by iPPSD2 (PHP1A), diagnosed because of family history, ectopic ossification or short stature and carrying a GNAS mutation...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28289136/estrogen-modulates-mesenchymal-epidermal-interactions-in-the-adult-nipple
#2
Hsing-Jung Wu, Ji Won Oh, Dan F Spandau, Sunil Tholpady, Jesus Diaz, Laura J Schroeder, Carlos D Offutt, Adam B Glick, Maksim V Plikus, Sachiko Koyama, John Foley
Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, specific pathways involved remain to be identified. By recombining cells from ventral skin of the K14-PTHrP transgenic mice with those from wild-type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially-expressed transcripts of the WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28257332/parathyroid-hormone-stimulates-adipose-tissue-browning-a-pathway-to-muscle-wasting
#3
Sandhya S Thomas, William E Mitch
PURPOSE OF REVIEW: Studying organ-to-organ communications (i.e. crosstalk) uncovers mechanisms regulating metabolism in several tissues. What is missing is identification of mediators of different catabolic conditions contributing to losses of adipose and muscle tissues. Identifying mediators involved in organ-to-organ crosstalk could lead to innovative therapeutic strategies because several disorders such as chronic kidney disease (CKD), cancer cachexia, and other catabolic conditions share signals of worsening metabolism and increased risk of mortality...
March 2, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28242308/molecular-characterisation-and-expression-of-parathyroid-hormone-related-protein-in-the-caudal-neurosecretory-system-of-the-euryhaline-flounder-platichthys-flesus
#4
Weiqun Lu, Yingying Jin, Jinling Xu, Michael P Greenwood, Richard J Balment
Parathyroid hormone-related protein (PTHrP) is a hypercalcemic factor in fish, but the source of circulating PTHrP remains unclear. In this study investigation of the caudal neurosecretory system (CNSS), considered one of major sources of PTHrP in fish, provided valuable insights into this regulatory system. We report pthrpa and pthrpb gene cloning, characterization, expression, and responses to low salinity and hypocalcemia challenge in flounder. The pthrpa and pthrpb precursors, isolated from a European flounder CNSS library, consist of 166 and 192 amino acid residues, respectively, with an overall homology of approximately 59...
February 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28217023/metabolic-bone-disease-in-the-context-of-metastatic-neuroendocrine-tumor-differentiation-from-skeletal-metastasis-the-molecular-pet-ct-imaging-features-and-exploring-the-possible-etiopathologies-including-parathyroid-adenoma-men1-and-paraneoplastic-humoral
#5
Rohit Ranade, Sandip Basu
Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan...
January 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28203174/richter-s-syndrome-with-hypercalcemia-induced-by-tumor-associated-production-of-parathyroid-hormone-related-peptide
#6
Naoki Watanabe, Hajime Yasuda, Soji Morishita, Yasuo Aota, Junichi Tomomatsu, Masaru Tanaka, Akimichi Ohsaka, Norio Komatsu
Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28178186/exogenous-pthrp-repairs-the-damaged-fracture-healing-of-pthrp-mice-and-accelerates-fracture-healing-of-wild-mice
#7
Yinhe Wang, Xin Fang, Chun Wang, Congzhu Ding, Hua Lin, Anlong Liu, Lei Wang, Yang Cao
Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone-related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/- mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods...
February 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28168064/hypercalcemia-of-malignancy-in-thymic-carcinoma-evolving-mechanisms-of-hypercalcemia-and-targeted-therapies
#8
Cheng Cheng, Jose Kuzhively, Sanford Baim
Here we describe, to our knowledge, the first case where an evolution of mechanisms responsible for hypercalcemia occurred in undifferentiated thymic carcinoma and discuss specific management strategies for hypercalcemia of malignancy (HCM). Case Description. We report a 26-year-old male with newly diagnosed undifferentiated thymic carcinoma associated with HCM. Osteolytic metastasis-related hypercalcemia was presumed to be the etiology of hypercalcemia that responded to intravenous hydration and bisphosphonate therapy...
2017: Case Reports in Endocrinology
https://www.readbyqxmd.com/read/28162969/parathyroid-hormone-directs-bone-marrow-mesenchymal-cell-fate
#9
Yi Fan, Jun-Ichi Hanai, Phuong T Le, Ruiye Bi, David Maridas, Victoria DeMambro, Carolina A Figueroa, Serkan Kir, Xuedong Zhou, Michael Mannstadt, Roland Baron, Roderick T Bronson, Mark C Horowitz, Joy Y Wu, John P Bilezikian, David W Dempster, Clifford J Rosen, Beate Lanske
Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28159062/abaloparatide-recombinant-human-pthrp-1-34-anabolic-therapy-for-osteoporosis
#10
REVIEW
Chee Kian Chew, Bart L Clarke
The treatment of osteoporosis is generally either by inhibition of bone resorption with antiresorptive agents or by stimulation of bone formation with anabolic agents. Currently, teriparatide (recombinant human parathyroid hormone 1-34 [rhPTH (1-34)]) is the only available approved anabolic agent in the U.S. Other anabolic agents are under investigation however. Abaloparatide is recombinant human parathyroid hormone-related peptide 1-34. This agent is an anabolic agent that appears more potent than teriparatide, and it may have more rapid onset of fracture reduction than teriparatide...
March 2017: Maturitas
https://www.readbyqxmd.com/read/28116542/the-hedgehog-signaling-pathway-is-repressed-during-the-osteogenic-differentiation-of-dental-follicle-cells
#11
C Morsczeck, A Reck, H C Beck
Dental follicle stem cells (DFCs) are precursor cells of alveolar osteoblasts, and previous studies have shown that the growth factor bone morphogenetic protein (BMP)2 induces the osteogenic differentiation of DFCs. However, the molecular mechanism down-stream of the induction of the osteogenic differentiation by BMP2 remains elusive. We investigated therefore the phosphoproteome of DFCs after the induction of the osteogenic differentiation with BMP2. In this study, phosphoproteins of the hedgehog "off" state were differentially expressed...
January 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28057913/humoral-hypercalcemia-in-uterine-cancers-a-case-report-and-literature-review
#12
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
#13
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
#14
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...
February 7, 2017: 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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