Etiketter

fredag 7 oktober 2016

Artikkeleita luuston metastaasista (etäpesäkkeistä)

https://www.ncbi.nlm.nih.gov/pubmed/27698885
Melanooma on hyvin harvinainen Aasiassa.
https://www.ncbi.nlm.nih.gov/pubmed/26846098 

 https://www.ncbi.nlm.nih.gov/pubmed/26785048

Duodecimilaiset kuvaavat mitä syöpä ja etäpesäke ovat.

https://www.kaikkisyovasta.fi/tietoa-syovasta/syovan-vaiheet-erilaistuminen-ja-levinneisyys/

Komplisoitumista osteokalsiinin aineenvaihdunnan teoriaan

https://www.ncbi.nlm.nih.gov/pubmed/27698897
Tämä löytö OC muodon vaikutuksesta luustometastaasivaiheessa tuo mieleen  warfariinin  hyödyn siitä hetkestä.

Mutta tässä täytyy ajatella että 1980-luvun jälkeen on myös negatiivisen koagulaatiokontrollin normaalisuuden merkitys käsitetty (plus  kehon rikkiaineenvaihdunnan liittyminen   sekä omat hepariinit ym). Warfariini sulkee K-vitamiiniaineenvaihdunnan kartan monet tiet pois.

Mikä  sitten on se K-vitamiinia tarvitsevissa peptideissä se  pahentava asia syövässä:  katsotaan toisesta suunnasta: Tässä alimmassa artikkelissa  on itse protrombiinipeptidin määrä noussut ja sen tromboottinen vaikutus myös noussut ja kudostekijää on kai  konsumoitunut. Tätä ei enää  normaali  negatiivinen koagulaatiokontrolli pystyne  tasapainottamaan ja ollaan trombogeenisella puolella ja muiden koagualaatiohäiriöitten puolella, ( jonka takia etsittiin seuraaviakin terapiamahdollisuuksia  ennen vuotta 2000.
Frenkel EP, Bick R.
In Vivo. 1998 Nov-Dec;12(6):625-8. Review.
4.
Garattini S.
Clin Exp Metastasis. 1987 Apr-Jun;5(2):105-24. Review. No abstract available.
Thromb Res. 1981 Nov 1;24(3):263-6.Cancer cell procoagulant: a novel vitamin K-dependent activity.
  • UUSINTA tietoa

Thromb Res. 2016 Apr;140 Suppl 1:S192. doi: 10.1016/S0049-3848(16)30176-1. Epub 2016 Apr 8.

PO-43 - Differential coagulation factor expression in neuroendocrine prostate cancer (PC), metastatic castrate-resistant PC, and localized prostatic adenocarcinoma.Choe H1, Sboner A1, Beltran H1, Nanus D1, Tagawa ST1.Abstract

INTRODUCTION:

Neuroendocrine prostate cancer (NEPC) is an aggressive late-stage variant of PC that is often androgen-receptor negative. Most clinicians believe the VTE rate with NEPC is higher than with standard metastatic castration-resistant PC (mCRPC), but NEPC tends to present with bulkier visceral disease and include platinum chemotherapy unlike standard PC. In many solid tumors, a more aggressive phenotype correlates with increased VTE risk and elevated expression of coagulation factors. We previously reported on the differential expression of thrombin and tissue factor (TF) in NEPC versus localized PC and benign prostate tissue with a small NEPC cohort (N=7), which showed overexpression of prothrombin and reduced expression of TF in NEPC.

AIM:

To compare the expression of coagulation factors of NEPC vs mCRPC (and localized PC control) in an expanded datase.

MATERIALS AND METHODS:

Fresh frozen tissue biopsies were collected and separated into three cohorts based on pathology: localized PC (N=68), standard mCRPC (N=32), and NEPC (N=21). RNA was isolated and next generation paired-end mRNA sequencing was performed on Illumina Sequencers. F2 Prothrombin (F2), tissue factor (F3), carboxypeptidase (CPB2), fibrinogen (FGG, FGA), PAR-1 (F2R), and PAR-2 (F2RL1) were compared by Wilcoxon tests.

RESULTS:

Prothrombin had significantly higher expression in NEPC versus standard mCRPC (p <0.001). NEPC trended towards higher expression of CPB2 (p=0.1) and lower expression of F3 (p=0.23) and F2RL1 (p=0.14) compared to mCRPC. Compared to localized PC, both types of advanced disease (NEPC and mCRPC) overexpressed F2, FGA, FGB, and CPB2 (p<0.001) and had decreased expression of F3 and F2RL1 (p <0.001).

CONCLUSIONS:

Prothrombin is reliably overexpressed in NEPC vs mCRPC and localized PC. Advanced disease (regardless of subtype) is associated with significantly higher expression of prothrombin, fibrinogen, and carboxypeptidase and lower expression of TF and PAR-2. It is possible that there may be PC-specific differences with aggressive disease associated with the thrombin axis vs the more common TF/PAR2 axis commonly seen in other advanced solid tumors. Further research is required to understand these differences in biology and resulting thrombotic and hemostatic outcomes.
© 2016 Elsevier Ltd. All rights reserved.
[PubMed] 
Artikkelit pohdittavaksi.  K-vitamiinin aineenvaihdunnan laajempi aspekti. Multifaktorielli asia.

Luun mineraalitiheys ja luuydinrasva. Matrixaines. Vertailuja

Eur J Endocrinol. 2016 Oct 5. pii: EJE-16-0448. [Epub ahead of print]

Marrow Adipose Tissue Spectrum in Obesity and Type 2 Diabetes Mellitus.

Abstract

OBJECTIVE:

To assess the association of bone mass and marrow adipose tissue (MAT) with other fat depots, insulin resistance, bone remodeling markers, adipokines and glucose control in type 2 diabetes and obesity.

DESIGN AND METHODS:

Cross-sectional study; comprised 24 controls (C), 26 obese (O) and 28 type 2 diabetes. Dual-energy X-ray absorptiometry was used to determine bone mineral density (BMD). Blood samples were collected for biochemical measurements. 1H Magnetic resonance spectroscopy was used to assess MAT in the L3 vertebra and abdominal magnetic resonance imaging was used to assess intrahepatic lipids, visceral (VAT) and subcutaneous adipose tissue. Regression analysis models were used to test the association between parameters.

RESULTS:

At all sites tested, BMD was higher in type 2 diabetes than in O and C subjects. The C group showed lower VAT values than the type 2 diabetes group and lower IHL than the O and type 2 diabetes groups. However, MAT was similar in the 3 groups. Osteocalcin and C-terminal telopeptide of type 1 collagen were lower in type 2 diabetes than in C and O subjects. Moreover, at all sites BMD was negatively associated with osteocalcin. No association was observed between MAT and VAT. No relationship was observed between MAT and HOMA-IR, leptin, adiponectin or Pref-1, but MAT was positively associated with glycated hemoglobin.

CONCLUSIONS:

MAT is not a niche for fat accumulation under conditions of energy surplus and type 2 diabetes is not associated with VAT or insulin resistance. MAT is associated with glycated hemoglobin.
[PubMed - as supplied by publisher]

Pyrofosfaatin vaikutus osteokalsiiniin, osteopontiiniin, alk. fosfataasiin ja kollageeni1:een.

PLoS One. 2016 Oct 4;11(10):e0163530. doi: 10.1371/journal.pone.0163530. eCollection 2016.

Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline Phosphatase Activity in Osteoblasts.

Abstract

Pyrophosphate is a potent mitogen, capable of stimulating proliferation in multiple cell types, and a critical participant in bone mineralization. Pyrophosphate can also affect the resorption rate and bioactivity of orthopedic ceramics. The present study investigated whether calcium pyrophosphate affected proliferation, differentiation and gene expression in early (MC3T3 pre-osteoblast) and late stage (SAOS-2 osteosarcoma) osteoblasts. Pyrophosphate stimulated peak alkaline phosphatase activity by 50% and 150% at 100μM and 0.1μM in MC3T3, and by 40% in SAOS-2. The expression of differentiation markers collagen 1 (COL1), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) were increased by an average of 1.5, 2, 2 and 3 fold, by high concentrations of sodium pyrophosphate (100μM) after 7 days of exposure in MC3T3. COX-2 and ANK expression did not differ significantly from controls in either treatment group. Though both high and low concentrations of pyrophosphate stimulate ALP activity, only high concentrations (100μM) stimulated osteogenic gene expression. Pyrophosphate did not affect proliferation in either cell type. The results of this study confirm that chronic exposure to pyrophosphate exerts a physiological effect upon osteoblast differentiation and ALP activity, specifically by stimulating osteoblast differentiation markers and extracellular matrix gene expression.
[PubMed - in process]
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Väitöskirjan keskiössä parametrina osteokalsiini (OC)

Bojan Tubic´. Bone and fat tissue in children and adolescents: studies with focus on osteocalcin.
ISBN: 978-91-9878-6.
http://hdl.handle.net/2077/43460

ABSTRACT:

The general AIM was to investigate the possible interplay between bone and fat tissue through clinical studies of children and adolescents.
 Osteocalcin (OC), a bone formation marker, has been proposed to act as a link between bone and energy metabolism in mice, but human data are inconclusive.
 The specific aims of this thesis were: 
(i) to clarify the role of OC in relation to weight, with focus on undercarboxylated OC (ucOC) and carboxylated OC (cOC); (ii) to gain insight on how obesity and underweight affect bone and fat tissue in children and adolescents and;
(iii) to study the effect of whole body vibration (WBV) on parameters of metabolic syndrome, bone metabolism and body composition in children with obesity. 

METHODOLOGY: Children and adolescents aged 2-24 years were included in the four studies.
 Study I and II were cross-sectional (case-control), and study III and IV were interventional with a 12-week follow-up, of which study IV was a randomized case-control study. Biochemical parameters were examined in all four studies. Bone mass and body composition were assessed by dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography, heel DXA and laser. Methods of intervention were high-energy diet in patients with anorexia nervosa (AN) and WBV in patients with obesity. 

RESULTS: Total OC and ucOC did not differ between normal-weight and overweight subjects; however, overweight subjects had lower cOC levels, and the measured OC forms did not correlate with insulin and glucose. Overweight children had increased bone mineral content (BMC) and bone mineral density (BMD) in comparison with normal-weight children, and there was a positive correlation between BMC, BMD and body mass index standard deviation score. 
Adiponectin was inversely correlated with BMC and BMD, and was an independent determinant of BMC and BMD.
 Patients with AN gained in weight and levels of all three forms of OC and BMC increased. The WBV did not result in any anthropometric changes; however, a reduction of sclerostin implies that WBV therapy has direct effects on bone mechanotransduction.

 CONCLUSIONS: This thesis could not confirm the hypothesis that OC has a positive effect on glucose and insulin homeostasis, although cOC was lower in obese subjects than in normal-weight subjects. The home-based WBV intervention study in young children with obesity did not result in any effect on weight, metabolic parameters or calcaneal bone mass