Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paget's disease usually is found in patients past the age of 40. Early presenting symptoms include headache, deafness, tinnitus, and pain due to radicular compression. The diagnosis is confirmed by radiographic features and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Bony overgrowth results in pressure on nearby soft tissues such as the brain, spinal cord, and certain peripheral nerves. The abnormally soft quality of the calvarial bone permits distortion by the weight of the brain. Dorsal inclination of the plane of the foramen magnum and the projection of the odontoid process into the posterior fossa lead to stretching of the brain stem over the odontoid process and the ventral margin of the foramen. Obstructive hydrocephalus may result. Sarcoma of the crainial vault may develop in cases of Paget's disease. Once cervicomedullary or spinal compression has occurred, surgical decompression may be necessary. Three drugs--calcitonin, disodium etidronate, and mithramycin--have been used with some benefit in the treatment of Paget's disease.
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PMID:Paget's disease and the nervous system. 21 14

The study of bone cancer has been difficult in part due to a lack of appropriate in vitro osteosarcoma model systems. The development of such systems is essential if a clearer understanding of the biology of and mechanisms behind the formation and progression of bone cancers is to be obtained. We report here the development of an in vitro model system which demonstrates important characteristics generally associated with osteosarcoma. The chick periosteal osteogenesis model was infected with the Fujinami Sarcoma Virus (FSV) containing the v-fps oncogene which encodes for a P140gag-fps protein-tyrosine kinase. Under the appropriate conditions FSV infected cultures developed bone and cartilaginous tissues which showed histopathological findings consistent with osteosarcoma. Biochemical data indicating massive increases in alkaline phosphatase activity, protein content, 3H-Thymidine incorporation as well as expression of active P140gag-fps confirm that transformation has occurred in FSV infected cultures. This novel in vitro model system should prove most useful in the study of bone cancer.
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PMID:In vitro transformation of osteoblasts: putative formation of osteosarcoma in vitro. 282 12

Purpose. The antimicrobial effect of a silver-coated tumor endoprosthesis has been proven in clinical and experimental trials. However, in the literature there are no reports concerning the effect of elementary silver on osteoblast behaviour. Therefore, the prosthetic stem was not silver-coated because of concerns regarding a possible inhibition of the osseointegration. The aim of the present study was to investigate the effect of 5-25 mg of elementary silver in comparison to Ti-6Al-4V on human osteosarcoma cell lines (HOS-58, SAOS). Methods. Cell viability was determined by measuring the MTT proliferation rate. Cell function was studied by measuring alkaline phosphatase (AP) activity and osteocalcine production. Results. In the HOS-58 cells, the AP activity was statistically significant (P < 0.05) higher at a supplement of 5-10 mg of silver than of Ti-6 Al-4V at the same doses. For both cell lines, a supplement above 10 mg of silver resulted in a reduced AP activity in comparision to the Ti-6 Al-4V group, but a statistically significant difference (P < 0.05) was observed at a dose of 25 mg for the SAOS cells only. At doses of 20-25 mg in the HOS-58 cells and 10-25 mg in the SAOS cells, the reduction of the proliferation rate by silver was statistically significant (P < 0.05) compared to the Ti-6 Al-4V supplement. Discussion. In conclusion, elementary silver exhibits no cytotoxicity at low concentrations. In contrast, it seems to be superior to Ti-6 Al-4V concerning the stimulation of osteogenic maturation at these concentrations, whereas at higher doses it causes the known cytotoxic properties.
Sarcoma 2007
PMID:The influence of elementary silver versus titanium on osteoblasts behaviour in vitro using human osteosarcoma cell lines. 1768 31

Purpose. To report the outcome of 37 patients with metastatic osteosarcoma entered into a large randomized trial (EOI 80831/MRC B002) comparing two different regimens of chemotherapy in patients with osteosarcoma.Methods. Patients with biopsy-proven osteosarcoma localized and metastatic, age 40 years or younger, were randomized to receive either two-drug treatment with doxorubicin/cisplatin (DOX 25 mg m(-2) day(-1) x 3 + DDP 100 mg m(-2) on day 1 q 3 weeks x 6 courses) or three-drug treatment comprising high-dose methotrexate (HDMTX 8 mg m(-2) administered every 4.5 weeks x 4 courses) given 10 days before DOX/DDP.Results. Twenty-four patients with metastatic disease received the two-drug arm treatment and 13 received three-drug treatment. Despite chance imbalance in numbers, there were no major differences in age, sex, primary site or performance status. Baseline alkaline phosphatase (AP) was elevated more frequently (96 vs 42%) in the two-drug arm. Twenty-one of 24 patients in the two-drug arm and 11/13 patients in the three-drug arm had evaluable primary tumors concurrent with metastases. Respective clinical response rates for the two- and three-drug arms were 48% and 40% for primary tumors, and 33% and 55% for metastases. Respective survivals at 2 and 4 years were 36% and 9% for the two-drug arm, and 69% and 52% for the three-drug arm, and survival was better for patients with normal AP at presentation. When adjusted for AP, survival was not significantly different between the two treatments (hazard ratio 0.52, 95% confidence interval 0.22-1.23, p = 0.14). There were three long-term survivors among the metastatic patients, all of whom received the three-drug therapy.Discussion. It is likely that random bias in the population (small numbers, imbalance in size of groups, uneven distribution of AP) accounts for the difference in outcome favoring the three-drug treatment in patients with metastatic disease. More reliance can be placed on the finding that disease-free and overall survival in the adjuvant component of this study (Bramwell et al., J Clin Oncol 1992; 10: 1579-91) were better after two-drug treatment.
Sarcoma 1997
PMID:A Randomized Comparison of two Short Intensive Chemotherapy Regimens in Children and Young Adults With Osteosarcoma: Results in Patients With Metastases: A Study of the European Osteosarcoma Intergroup. 1852 Dec 18

A middle aged chronic alcoholic presented with deep jaundice, markedly enlarged and tender spleen with leukoerythroblastic blood picture and bone marrow biopsy showing mild fibrosis. He was tested negative for HIV, hepatitis B and C viruses. Besides very high serum bilirubin, alkaline phosphatase was raised four times the normal value. Contrast enhanced CT showed enlarged spleen and liver with multiple heterogenous lesions in spleen and tiny hypo-dense lesions in liver. In hospital, he developed haemolytic uraemic syndrome and succumed to his illness. At autopsy spleen weighed 5200 gms and variegated in appearance due to large areas of necrosis and whitish tumour nodules. Histology revealed morphology of an angiosarcoma. Liver was also infiltrated by the tumour mainly in and around portal tract areas.
Sarcoma 2003
PMID:Splenic angiosarcoma presenting with jaundice, ascites and bone marrow fibrosis. 1852 85

Strontium ralenate is a new anti-osteoporosis agent. The cellular and molecular mechanism underlying the anabolic effect of strontium on bone remains to be elucidated. Osteoblasts, the main bone forming cells are known to be derived from bone marrow mesenchymal stem cells (MSCs). The present study therefore aimed to investigate the possible effects of strontium on MSCs and signaling pathways possibly involved. It was firstly demonstrated that strontium treatment significantly increased osteoblast-related gene expression and alkaline phosphatase (ALP) of osteogenic-differentiating MSCs. Accompanying the enhanced osteogenic differentiation, the increased phosphorylation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 was detected in strontium-treated MSCs. PD98059 and SB203580, selective inhibitors of ERK1/2 kinase and p38, attenuated the effect of strontium on osteogenesis. Furthermore, it was demonstrated that Rat Sarcoma viral oncogene homolog (RAS), an upstream regulator of ERK1/2 and p38, was activated by strontium treatment and siRNA-mediated Ras knockdown inhibited strontium-stimulated expression of osteogenic markers. Finally, the transcriptional activity and phosphorylation level of Runx2 was significantly increased in response to strontium treatment in MSCs. PD98059 and Ras siRNA inhibited the effect of strontium on Runx2 activation. Taken together, these results indicated that strontium can promote osteogenic differentiation of MSCs through activating the Ras/MAPK signaling pathway and the downstream transcription factor Runx2.
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PMID:Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway. 1925 11