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)

A female presenting multiple osteoma cutis lesions without underlying endocrinological disturbance was studied. Histologically, lesions revealed true bone formation with multiple osteoblastic cells. This was confirmed by demonstrating high alkaline phosphatase activity and osteonectin expression in osteoma cutis lesions. Interestingly, tenascin and type III procollagen were in close association to bony lesions, indicating that these matrix proteins may be somehow involved in bone formation. In situ hybridization revealed fibroblastic cells around bony lesions, which actively deposited type I collagen and osteonectin. One of the activators of bone formation, TGF beta, was also present in some osteoblastic cells. The results thus indicate that in osteoma cutis, fibroblasts have the ability to differentiate into osteoblastic cells, which have some properties of osteoblasts, such as high alkaline phosphatase activity and a high expression of osteonectin.
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PMID:A study of bone formation in osteoma cutis employing biochemical, histochemical and in situ hybridization techniques. 135 50

Osteomas (dense compact neoplasms of mature bone tissue) are rare in nearly all strains and stocks of mice. Of 224 Him:OF1 mice maintained until natural death or until terminally ill, 116 (51.8%) had one or more osteomas. Osteomas had a predilection for the skull and the larger bones of the limbs. Plasma alkaline phosphatase concentrations were elevated significantly in osteoma-bearing mice (446 +/- 153 U/liter versus 206 +/- 65 U/liter in age-matched controls without osteomas). Only very large osteomas resulted in clinical signs, and longevity was not shortened. Histologic examination showed clearly separated dense bony tissue irregularly arranged and forming a mosaic pattern, with distinct cement lines and medullary spaces filled with fibroreticular connective tissue. Electron microscopic examination revealed virus-like structures in osteoblasts, osteocytes, and fibroblasts and in the place of remnants of necrotic cells.
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PMID:Multiple osteomas in mice. 794 Dec 31

Although the therapeutic outcome of osteosarcoma patients has improved dramatically within the last 20 years because of combined neoadjuvant chemotherapy and surgery, the problem of drug resistance remains. Thus far, markers that can predict the response to chemotherapy at the time of biopsy are not available. Heat shock proteins (hsp) 60, 72, and 73 have been shown to play a role in tumor immunity, and our study investigated their expression in human osteosarcomas and nonmalignant bone tumors before neoadjuvant chemotherapy. Immunohistochemical evaluations of hsp expression was performed on paraffin-embedded sections of 45 patients (17 female, 28 male, aged 6.5 to 62 years; mean, 19.4 years) with high-grade osteosarcoma at the time of biopsy, before preoperative chemotherapy. These results were correlated to histological response to chemotherapy, tumor size, age, alkaline phosphatase serum levels, and duration of symptoms. Thirty-four patients (15 male, 19 female, mean age 27 years) with osteoblastoma, osteoid-osteoma, or fibrous dysplasia served as nonmalignant controls. Hsp60 was uniformly found in the cytoplasm of both benign and malignant bone tumors. Nuclear hsp73 expression quantitatively increased in osteosarcoma cells. Hsp72 was significantly overexpressed in osteosarcomas (17 of 45, 38%) compared with nonmalignant bone tumors (1 of 34, 2.9%; P < .001). Hsp72-positive osteosarcomas responded better to neoadjuvant chemotherapy than hsp72-negative cases (P < .001), co-express hsp60, and correlate with higher tumor size (P < .005) and location in the distal femur. No differences were observed relative to age, gender, duration of symptoms, alkaline phosphatase levels, or hsp73 expression between hsp72-positive and hsp72-negative tumors. Hsp72 expression seemed to be a predictive immunohistochemical marker for osteosarcoma, because it is the first marker to prospectively correlate to response to neoadjuvant chemotherapy. It therefore, may be of importance in preoperative therapy regimens for nonresponding high-risk patients.
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PMID:Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy. 978 40

Cell lines were established by a two-step method from osteomas which had been induced by infection of mice with RFB MuLV, a bone-pathogenic, replication-competent murine retrovirus. The benign tumors, consisting of mature lamellar bone and surrounded by a thin periosteum, were cultured on sponges of denatured collagen type I fibres for up to 4 weeks. At this time osteoma cells had grown into the collagenous matrix. After release and further cultivation in monolayers, the cell lines established from these cultures varied in morphology; they expressed T1, collagen type I and type III, alkaline phosphatase, osteonectin and osteopontin mRNAs at variable levels, but not osteocalcin/BGP. They also showed alkaline phosphatase activity, but lacked responsiveness to parathyroid hormone. All cell lines established from infected mice expressed retroviral and c-myc mRNA and viral protein. In contrast to cells from control mice they showed an extended life span in culture. After growth in a three-dimensional (3-D) collagen sponge culture the cells formed an extracellular matrix containing collagen type I, alkaline phosphatase and osteocalcin/BGP. These data indicate that the two-step method facilitates the establishment of osteoblast-like cell lines from osteomas and calvaria of old mice, and provides means for further analyses of retrovirus-induced skeletal pathogenesis and bone induction.
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PMID:Establishment and characterization of osteoblast-like cell lines from retrovirus (RFB MuLV)-induced osteomas in mice. 981 Jul 4

Despite advances in nuclear medicine, bone scintigraphy remains an important imaging technique. It is sensitive in detecting stress fractures and bone metastases and can assess suspected injury that is difficult to see on plain films (e.g., rib fracture). Scintigraphy is useful in evaluating new symptoms, response to therapy, and prognosis in patients with known malignant tumor. In patients with low back pain, the technique can determine the age of fractures to help identify osteoporosis and can uncover other causes of the pain (e.g., spondylolysis, arthritis). When Paget's disease is suggested by unexplained bone pain or an elevated serum alkaline phosphatase level, bone scintigraphy is a useful screening test. Combined with other appropriate nuclear medicine studies, it helps in early identification and localization of osteomyelitis. Scintigraphic scans can provide a general indicator of malignant versus benign disease (according to the amount of lesion activity seen) and may produce characteristic findings in certain primary tumors (e.g., osteoid osteoma) that are difficult to evaluate with other methods.
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PMID:When to use bone scintigraphy. It can reveal things other studies cannot. 982 85

Intracortical osteosarcoma is the rarest variant of osteosarcoma, occurring within, and usually confined to, the cortical bone. Oncogenic osteomalacia, or rickets, is an unusual clinicopathologic entity in which vitamin D-resistant osteomalacia, or rickets, occurs in association with some tumors of soft tissue or bone. We present a case of oncogenic rickets associated with intracortical osteosarcoma of the tibia in a 9-year-old boy, whose roentgenographic abnormalities of rickets disappeared and pertinent laboratory data except for serum alkaline phosphatase became normal after surgical resection of the tumor. Histologically, the tumor was an osteosarcoma with a prominent osteoblastic pattern. An unusual microscopic feature was the presence of matrix mineralization showing rounded calcified structures (calcified spherules). Benign osteoblastic tumors, such as osteoid osteoma and osteoblastoma, must be considered in the differential diagnosis because of the relatively low cellular atypia and mitotic activity of this tumor. The infiltrating pattern with destruction or engulfment of normal bone is a major clue to the correct diagnosis of intracortical osteosarcoma. The co-existing radiographic changes of rickets were due to the intracortical osteosarcoma.
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PMID:Intracortical osteoblastic osteosarcoma with oncogenic rickets. 1006 74

A 62-year-old Asian woman presented with multiple small, rock-hard papular lesions on her face (Figure). She had no previous history of acne vulgaris or cutaneous malignancy. She had been diagnosed with breast cancer in 1995 and was treated with left lumpectomy followed by combination chemotherapy consisting of cyclophosphamide, 5-fluorouracil, and methotrexate. In 1995, at age 50, she also began therapy with systemic alendronate to treat osteoporosis. Within 1 year, she noticed the development of asymptomatic indurated dermal papules on her cheeks. Topical treatment with 12% lactic acid lotion did not improve her condition. Clinical examination revealed numerous 1- to 2-mm, brown dermal nodules on the malar cheeks bilaterally. Normal laboratory data included complete blood cell count, alkaline phosphatase, serum calcium, and serum phosphate. A lesional punch biopsy from the left cheek revealed lamellar bone within the dermis. Correlation of the clinical presentation, laboratory data, and pathology established the diagnosis of multiple miliary osteoma cutis of the face.
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PMID:Multiple miliary osteoma cutis of the face after initiation of alendronate therapy for osteoporosis. 2198 Jul 13