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Prospective observational study for the impact of short-term periodic intravenous steroid premedication for gastrointestinal cancer chemotherapy on bone metabolism.

ABSTRACT: Primary outcome(s): To investigate the variations of bone mineral densities (DEXA) and bone turnover markers (NTX and BAP) between baseline and 16 weeks after.

DISEASE(S): Gastrointestinal Cancer: Colorectal Cancer, Non-colorectal Cancer (gastroesophageal, Pancreatic, And Biliary Tract Cancer)

PROVIDER: 2626430 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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A multicenter prospective study on the efficacy and safety of denosumab in gastrointestinal cancer patients receiving short-term periodic steroid premedication of chemotherapy-induced nausea and vomiting (ESPRESSO-02/HGCSG1602)

Project description:Interventions: The dose of denosumab (Prolia) is 60mg administered as a single subcutaneous injection within a week before the induction of chemotherapy. All participants should receive adequate calcium and vitamin D supplementation. Primary outcome(s): To investigate the efficacy of denosumab for preventing a bone mineral density reduction 16 weeks after induction of chemotherapy. Study Design: Single arm Non-randomized

| 2639108 | ecrin-mdr-crc

Mapping the tumor microenvironment response to bone mineral content

Project description:Decreased mineral density is a risk factor for skeletal pathologies including bone metastasis, the leading cause of mortality in patients with advanced breast cancer, but the underlying mechanisms are poorly understood. While reduced mineral density can drive pathological bone remodeling via direct effects on select cell types, indirect effects due to broad changes of the microenvironment may be similarly important. However, how bone mineral content affects microenvironmental heterogeneity remains to be elucidated. Here, we leverage decellularized bone matrices with varied mineral content in combination with single-cell RNA-sequencing to study how reduced bone mineral content affects microenvironmental complexity and tumor growth. We performed single-cell RNA sequencing on implanted decellularized bovine bone scaffolds in which the mineral was either maintained at physiological levels or removed to simulate scenarios of impaired bone mineralization as, for example, present during aging. Using this approach, we explored the heterogeneous stromal response to varied bone mineral content in both an immunocompromised and immunocompetent, syngeneic mouse model in the presence and absence of cancer cells.

2024-03-04 | GSE256109 | GEO

Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HuEx-1_0-st-v2)

Project description:Comparison of circulating monocytes from pre- and postmenopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix 1.0 ST arrays in 73 Caucasian females (age: 47-56) with extremely high (mean ZBMD =1.38, n=42, 16 pre- and 26 postmenopausal subjects) or low hip BMD (mean ZBMD=-1.05, n=31, 15 pre- and 16 postmenopausal subjects). Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects.

2016-06-01 | E-GEOD-56814 | biostudies-arrayexpress

Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

Project description:<p>Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.</p>

2021-11-23 | MTBLS3725 | MetaboLights

Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HG-U133A)

2016-06-01 | GSE56815 | GEO

Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HuEx-1_0-st-v2)

2016-06-01 | GSE56814 | GEO

Transcription profiling of bone biopsies from postmenopausal females identifies 8 genes highly associated with bone mineral density

Project description:Postmenopausal females (50 85 years) representing a wide range of Bone mineral densities (BMDs) were consecutively registered, excluding persons who had diseases and medications known to affect bone remodeling. Low energy fracture(s) occurred in 32 (38 %). Trans-iliacal bone biopsies (84) were submitted to Affymetrix microarray expression analysis to study the relationship between BMD or osteoporosis and gene expression.

2009-11-12 | E-MEXP-1618 | biostudies-arrayexpress

Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HG-U133A)

Project description:Comparison of circulating monocytes from pre- and postmanopausal females with low or high bone mineral density (BMD). Circulating monocytes are progenitors of osteoclasts, and produce factors important to bone metabolism. Results provide insight into the role of monocytes in osteoporosis. We identify osteoporosis genes by microarray analyses of monocytes in high vs. low hip BMD (bone mineral density) subjects. Microarray analyses of monocytes were performed using Affymetrix HG-133A arrays in 80 Caucasian females, including 40 high (20 pre- and 20 postmanopausal) and 40 low hip BMD (20 pre- and 20 postmanopausal) subjects

2016-06-01 | E-GEOD-56815 | biostudies-arrayexpress

Acid bone lysates: what we eliminate by preparing demineralized bone matrix

Project description:Demineralized bone matrix is a widely used allograft where not only the inorganic mineral but also embedded growth factors are removed by hydrochloric acid. The cellular response to the growth factors released during the preparation of demineralized bone matrix, however, has not been studied. Here we investigated the in vitro impact of acid bone lysates (ABL) prepared from porcine cortical bone chips on oral fibroblasts. Proteomic analysis of ABL revealed a large spectrum of bone-derived proteins including TGF-β1. Whole genome microarrays and RT-PCR together with the pharmacologic blocking of TGF-β receptor type I kinase with SB431542 showed that ABL activates the TGF-β target genes interleukin 11, proteoglycan 4, and NADPH oxidase 4. Interleukin 11 expression was confirmed at the protein level by ELISA. Immunofluorescence and Western blot showed the nuclear localization of Smad2/3 and increased phosphorylation of Smad3 with ABL, respectively. This effect was independent of whether ABL was prepared from mandible, calvaria or tibia. ABL prepared with 0.1 N HCL was most effective compared to lysates obtained with 0.01 N and also 1.0 N HCl. These results demonstrate that TGF-β is a major growth factor that is removed upon the preparation of demineralized bone matrix.

2018-11-04 | PXD010145 | Pride

Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density [Osteoclast_0_3days]

Project description:The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored the International Mouse Phenotyping Consortium (IMPC) for the analysis of skeletal data from 3,974 mutant strains for bone mineral density (BMD), a measure that is frequently altered in a range of bone pathologies including osteoporosis. A total of 200 genes were found to significantly affect BMD. This gene pool comprised 141 genes that were previously not known to have a function in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 BMD genes also caused skeletal abnormalities. Further, evidence suggested a direct role for several of the identified BMD genes in osteoclasts and osteoblasts, and candidate genes for further investigation were prioritized. Overall, the results add novel pathophysiological and molecular insight into bone health and disease

2021-01-12 | GSE158150 | GEO

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