Abstract：
:The five-year survival rate for primary bone cancers is ~ 70% while almost all cases of secondary metastatic bone cancer are terminal. Hypoxia, the deficiency of oxygen which occurs as the rate of tumour growth exceeds the supply of vascularisation, is a key promoter of tumour progression. Hypoxia-driven effects in the primary tumour are wide ranging including changes in gene expression, dysregulation of signalling pathways, resistance to chemotherapy, neovascularisation, increased tumour cell proliferation and migration. Paget's seed and soil theory states that for a metastasising tumour cell 'the seed' it requires the correct microenvironment 'soil' to colonise. Why and how metastasising tumour cells colonise the bone is a complex and intriguing problem. However, once present tumour cells are able to disrupt bone homeostasis through increasing osteoclast activity and downregulating osteoblast function. Osteoclast resorption releases growth factors from the bone matrix that subsequently contribute to the proliferation of invasive tumour cells creating the vicious cycle of bone loss and metastatic cancer progression. Recently, we have shown that hypoxia increases expression and release of lysyl oxidase (LOX) from primary mammary tumours, which in turn disrupts bone homeostasis to favour osteolytic degradation to create pre-metastatic niches in the bone microenvironment. We also demonstrated how treatment with bisphosphonates could block this cancer-induced bone remodelling and reduce secondary bone metastases. This review describes the roles of hypoxia in primary tumour progression to metastasis, with a focus on key signalling pathways and treatment options to reduce patient morbidity and increase survival.
journal_name
Calcif Tissue Intjournal_title
Calcified tissue internationalauthors
Cox TR,Erler JT,Rumney RMHdoi
10.1007/s00223-017-0352-6subject
Has Abstractpub_date
2018-02-01 00:00:00pages
163-173issue
2eissn
0171-967Xissn
1432-0827pii
10.1007/s00223-017-0352-6journal_volume
102pub_type
杂志文章,评审abstract：:Changes in the acidity of osteoclasts were evaluated by direct measurement of the fluorescent intensity of osteoclasts exposed to acridine orange, a fluorescent weak base which becomes concentrated in acid-containing subcellular compartments. Parathyroid hormone (PTH) produced dose-dependent increases in fluorescent i...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02554924
更新日期：1985-12-01 00:00:00
abstract：:Energy-dispersive X-ray microanalysis was used to determine calcium/phosphorous (Ca/P) ratios in undecalcified teeth, and the sulfur (S) content of dentin of decalcified teeth from normal patients and patients with familial hypophosphatemia, in an attempt to determine the effect of phosphorus deficiency. The results s...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02555886
更新日期：1990-12-01 00:00:00
abstract：:The purpose of the present study was to determine if the type of dietary fat can modify the fatty acid composition and arachidonic acid levels in the alveolar bone phospholipids. Three groups of rats were fed nutritionally adequate semipurified diets containing different lipids: 10% corn oil (control, group I, rich in...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF01351838
更新日期：1993-11-01 00:00:00
abstract：:Quantitative computed tomography (QCT) was compared to dual X-ray absorptiometry (DXA) measured in the lumbar spine of 508 European women defined as normal without fracture (NoF), or osteoporotic (OP), with either vertebral fracture (VF), or peripheral fracture (PF). The correlations between QCT and DXA BMD measuremen...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02678144
更新日期：2001-02-01 00:00:00
abstract：:To compare the ability of the bone mineral density (BMD) at the distal forearm, collagen I alpha 1 (COLIA1) polymorphism, and ultrasound stiffness to identify individuals with increased risk of wrist fracture, we studied 183 postmenopausal Czech women with a wrist fracture and 178 postmenopausal controls, ages 45-70 y...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-004-0134-9
更新日期：2005-02-01 00:00:00
abstract：:The accompanying article by Drs. Lian and Stein describes current thinking on how genes are organized in the nucleus and suggests that subnuclear localization is critical for the control of gene expression in bone. In particular, it is proposed that a major function of the osteoblast transcription factor, Runx2, is to...
journal_title：Calcified tissue international
pub_type： 评论,杂志文章,评审
doi：10.1007/s00223-002-1053-2
更新日期：2003-06-01 00:00:00
abstract：:The type IA osteogenesis imperfecta (OI) phenotype is characterized by multiple fractures, blue sclerae, and minimal skeletal deformity without dentinogenesis imperfecta. The object of this study was to determine the effect of treatment with intravenous pamidronate (30 mg) every 3 months on bone density and bone histo...
journal_title：Calcified tissue international
pub_type： 临床试验,杂志文章
doi：10.1007/s00223-001-1055-5
更新日期：2003-02-01 00:00:00
abstract：:At 4 and 24 hours after injection of (35S)sulfate, there were 22-67% fewer silver grains on conventionally fixed sections than on sections fixed by cryotechniques. Differences were smaller when (3H) glucosamine was chosen as precursor. The number of silver grains increased between 4 and 24 hours in predentine and in a...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02557834
更新日期：1985-09-01 00:00:00
abstract：:Sarcopenia is now clinically defined as a loss of muscle mass coupled with functional deterioration (either walking speed or distance or grip strength). Based on the FRAX studies suggesting that the questions without bone mineral density can be used to screen for osteoporosis, there is now a valid simple questionnaire...
journal_title：Calcified tissue international
pub_type： 杂志文章,评审
doi：10.1007/s00223-015-0022-5
更新日期：2016-04-01 00:00:00
abstract：:We compared the cytotoxic effects of alendronate (ALN) and incadronate (YM175) on isolated rabbit osteoclasts in vitro and on rats in vivo. In the in vitro experiment, each bisphosphonate was added to the culture of isolated osteoclasts at the final concentration of 3 x 10(-5), 3 x 10(-4), or 3 x 10(-3) M, and the amo...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s002239900505
更新日期：1998-08-01 00:00:00
abstract：:We hypothesized that reactive oxygen species play an important role in avascular/ischemic osteonecrosis. When isolated chick osteocytes were cultured with hydrogen peroxide, annexin V binding, which is the earliest marker of apoptosis, increased in a dose-dependent fashion. Hydrogen peroxide also induced the activatio...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-001-1110-2
更新日期：2002-09-01 00:00:00
abstract：:Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental...
journal_title：Calcified tissue international
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1007/s002230001146
更新日期：2000-10-01 00:00:00
abstract：:Cartilage oligomeric matrix protein (COMP) is a macromolecule of yet unknown function with restricted distribution among tissues. In the present study, the ultrastructural localization of COMP in porcine immature joint cartilage and growth plate cartilage was semiquantitatively delineated. Tissues were fixed in a mixt...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s002239900278
更新日期：1997-06-01 00:00:00
abstract：:The bone mineral density (BMD) of the spine was measured in the posteroanterior (PA) and lateral projections as well as the total body BMD in 447 black and white women. The lateral projection is comprised predominantly of cancellous bone whereas the total body BMD is predominantly cortical bone, and the PA spine is in...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s002239900653
更新日期：1999-07-01 00:00:00
abstract：:Osteoclastic bone resorption can be induced within the auditory bulla of the Mongolian gerbil by minute increases in air pressure. The objective of this study was to determine the rate at which osteoclasts are induced in areas of resorption and to compare the rate of osteoblast recruitment. Stainless steel tubes were ...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02556026
更新日期：1989-11-01 00:00:00
abstract：:It has long been thought that collagen fibers within the bone matrix are deposited in an aligned pattern that channels mineral growth. If this model of bone structure is correct, both organic and inorganic phases of bone should have similar elastic anisotropy. Using an acoustic microscope, we measured longitudinal and...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF00299319
更新日期：1994-11-01 00:00:00
abstract：:Osteoporosis is characterized by low bone mass and a deterioration of bone architecture and likely is influenced by genetic factors. The ovariectomized (OVX) mouse is well suited for osteoporosis research, as shown to date by cross-sectional studies. Here, we investigate longitudinal changes by in vivo micro-computed ...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-008-9150-5
更新日期：2008-07-01 00:00:00
abstract：:The severest long-term complications of orthopedic joint-prostheses are associated with loosening of the implant-bone interface, due to adverse reactions in bone and subsequent weakening of the connection between the two materials. Mechanical stresses, caused by joint loading, play a key role in the adaption of interf...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02406143
更新日期：1984-01-01 00:00:00
abstract：:The metacarpal bone mineral density (BMD) and metacarpal index (MCI) of the second metacarpal bone were measured by computed X-ray densitometry (CXD) (Teijin Ltd., Tokyo), which we have established with the development of microdensitometry of radiographs. In this study, we evaluated the basic attributes of this CXD me...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF00299308
更新日期：1994-11-01 00:00:00
abstract：:Urinary pyridinoline (pyr) and deoxypyridinoline (dpyr) are new markers for bone resorption, and serum osteocalcin reportedly indicates osteoblastic activity. Recently, a new ultrasound bone densitometer instrument has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS...
journal_title：Calcified tissue international
pub_type： 临床试验,杂志文章
doi：10.1007/BF00298555
更新日期：1994-12-01 00:00:00
abstract：:The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on...
journal_title：Calcified tissue international
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00223-012-9577-6
更新日期：2012-04-01 00:00:00
abstract：:The effect of the configuration of porous cylindrical hydroxyapatite (HA) scaffold and laminin preparation of the scaffold on bone formation was estimated. HA scaffolds with a hollow center of 2 or 4 mm in diameter and those without a hollow center were used. The scaffolds were immersed in laminin solution or in cultu...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-008-9157-y
更新日期：2008-08-01 00:00:00
abstract：:Differences in trabecular and cortical bone loss have been demonstrated clinically, but differences in bone loss at different skeletal sites remain unclear. We examined regional variations in bone loss histomorphometrically in two strains of mice in which osteopenia progresses spontaneously: tiptoe-walking Yoshimura (...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s002239900455
更新日期：1998-05-01 00:00:00
abstract：:The evidence now strongly supports a central role for oestrogen in the maintenance of the normal female skeleton. Loss of endogenous oestrogen leads to a period of accelerated bone loss which can be prevented with appropriate oestrogen replacement. The route of administration is not important provided adequate dosages...
journal_title：Calcified tissue international
pub_type： 杂志文章,评审
doi：10.1007/BF02555090
更新日期：1991-01-01 00:00:00
abstract：:Connective tissue diseases, including osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS), exhibit a high degree of clinical and genetic heterogeneity. We report two sisters with blue sclerae, joint hypermobility and hearing loss. Whole-exome sequencing identified two compound heterozygous ZNF469 loss-of-fun...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-020-00721-3
更新日期：2020-09-01 00:00:00
abstract：:This study revealed the distinguished changes of preferential orientation of collagen and apatite and Young's modulus in two different types of osteoporotic bones compared with the normal bone. Little is known about the bone material properties of osteoporotic bones; therefore, we aimed to assess material properties i...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-018-0508-z
更新日期：2019-04-01 00:00:00
abstract：:The mechanism whereby liposomal entrapment enhances the hypocalcemic effect of calcitonin (CT) was evaluated in the rat. Phosphatidylcholine (PC) and PC plus cholesterol (PCC) preparations of large multilammelar vesicles (MLV) and small unilammelar vesicles (SUV) were used to entrap human calcitonin (hCT). The effect ...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02555889
更新日期：1990-12-01 00:00:00
abstract：:During mechanical unloading, endothelial cells reduce osteogenesis and increase bone resorption. Here we describe the feedback response of endothelial cells to unloaded osteoblasts. Primary endothelial cells, ex vivo mouse aortic rings and chicken egg yolk membranes were incubated with conditioned medium from mouse pr...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-018-0496-z
更新日期：2019-03-01 00:00:00
abstract：:Using a combination of gel filtration and DEAE-cellulose chromatography, together with small-scale preparative polyacrylamide gel electrophoresis, we isolated five proteins (amelogenins) from demineralized bovine fetal dental enamel matrix. These purified proteins were characterized by amino acid analysis and gel elec...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/BF02441163
更新日期：1979-03-13 00:00:00
abstract：:Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and bone archi...
journal_title：Calcified tissue international
pub_type： 杂志文章
doi：10.1007/s00223-015-0091-5
更新日期：2016-03-01 00:00:00
