Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purification of human bone alkaline phosphatase, derived from human osteosarcoma tissue, has been carried to electrophoretic homogeneity. The purification procedure involved three major steps: (1) chromatography on hydroxylapatite; (2) ion exchange chromatography; and (3) gel filtration. The resultant purified enzyme is a glycoprotein, has a molecular weight of approximately 80,000 (consistent with previous reports for the bone isoenzyme), and is characteristically inhibited by modest heat (56 degrees C, 30 min) and L-homoarginine but not by L-phenylalanine. The isolation and purification procedure described can lead to the production of significant amounts of highly purified bone alkaline phosphatase. Purified ALP can be used for an analysis of minor structural differences that appear to exist between the bone, liver and kidney isoenzymes. Such information could lead to the development of a clinical diagnostic procedure specifically for bone alkaline phosphatase.
 ...
PMID:Purification of bone alkaline phosphatase from human osteosarcoma. 350 97

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.
 ...
PMID:Control of primary osteosarcoma with chemotherapy. 387 85

An organ-specific alkaline phosphatase inhibitor, L-homoarginine, at 44.5 mM concentration inhibited [3H]thymidine uptake by C3H/He mouse osteosarcoma (OS) cells, while L-arginine, L-phenylalanine, and glycine had little effect on the uptake. This inhibitory effect of L-homoarginine persisted even after the cells were washed free of the amino acid with fresh media. L-Homoarginine did not affect [3H]thymidine uptake by mouse myeloma MOPC 104E cells. In long-term culture, 22.3 mM L-homoarginine inhibited proliferation of OS cells. L-Arginine at the same concentration inhibited the proliferation to a lesser extent. On the other hand, L-phenylalanine and glycine did not affect in vitro proliferation of OS cells. When the same number of viable OS cells was inoculated s.c. after culturing the 24 hr with 44.5 mM L-homoarginine or L-arginine, the tumor growth in mice given injections of L-homoarginine (but not L-arginine)-treated cells was delayed markedly. Electron microscopic studies indicated that the inhibiting effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, biochemical assay for acid phosphatase of cell homogenates demonstrated a 2-fold increase of activity in L-homoarginine-treated cells when compared to controls and L-arginine-treated cells. Thus, L-homoarginine inhibits proliferation and alkaline phosphatase activity of mouse OS cells and appears to increase acid phosphatase activity in synthesis of lysosomal granules.
 ...
PMID:Inhibitory effect of L-homoarginine on murine osteosarcoma cell proliferation. 617 11

An organ-specific alkaline phosphatase (AIP) inhibitor, L-homoarginine at 44.5 mM concentration inhibited 3H-thymidine uptake by mouse C3H/He osteosarcoma (OS) cells, while L-arginine, L-phenylalanine and L-glycine had little effect on the uptake. This inhibitory effect by L-homoarginine persisted even after the cells were washed free of the amino acid with fresh media. L-homoarginine did not affect 3H-thymidine uptake by mouse myeloma MOPC 104E cells. In the long-term culture, 22.3 mM L-homoarginine inhibited proliferation of OS cells. L-Arginine at the same concentration inhibited the proliferation to a lesser extent. On the other hand, L-phenylalanine and L-glycine did not affect in vitro proliferation of OS cells. When similar numbers of viable OS cells were inoculated s. c. after culturing with 44.5 mM L-homoarginine or L-arginine for 24 hr, the tumor growth in mice injected with L-homoarginine (but not L-arginine) treated cells was delayed markedly. Electron microscopic studies indicated that the inhibitory effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, a biochemical assay of acid phosphatase (AcP) of the cell homogenates demonstrated two-fold increase of the activity in L-homoarginine treated cells when compared to the controls and L-arginine treated cells. Thus, L-homoarginine inhibits proliferation and AIP activity of mouse OS cells and appears to promote cell differentiation as evidenced by the increased synthesis of cytoplasmic granules and acid phosphatase activity.
 ...
PMID:[Inhibitory effect of L-homoarginine on murine osteosarcoma cell proliferation]. 619 5

A unique case of a 15-year-old boy with complete paraplegia due to the compression of osteogenic sarcoma at the fourth thoracic vertebra is presented. Because of the difficulty of surgical treatment, he was treated merely by the arterial infusion of Adriamycin (doxorubicin) and systemic chemotherapy in conformity with the cyclophosphamide, Oncovin (vincristine), methotrexate, phenylalanine mustard, Adriamycin (doxorubicin) ( COMPADRI )-III regimen. The patient regained normal function, and has been disease-free without any neurologic deficit for 6 years. There appears to be some hope for cure using chemotherapy only in otherwise unpromising patients.
 ...
PMID:Osteogenic sarcoma of the fourth thoracic vertebra. Long-term survival by chemotherapy only. 658 74

We have found that the gamma-carboxyglutamic acid (GLA)-containing protein from bone (BGP, osteocalcin) has chemotactic activity in vitro for a number of cells which are found adjacent to endosteal bone surfaces in vivo. Using the Boyden chamber technique for measuring cell chemotaxis in vitro, we have shown that BGP is chemotactic for cultured human breast cancer cells, human and mouse monocytes, and for cultured rat osteosarcoma cells which have the characteristics of osteoblasts. The migration of these cells in response to BGP is undirectional and not due to spontaneous or random migration. A synthetic peptide (Phe-Tyr-Gly-Pro-Val), which is identical to the carboxy-terminal peptide cleaved from BGP when digested by trypsin, is also chemotactic for the same cells. BGP retains its chemotactic activity after conversion of the gamma-carboxyglutamic acid residues to glutamic acid, indicating that this biological effect requires neither gamma-carboxyglutamate nor the ability of BGP to bind calcium. Since BGP is released from bone during states of increased bone turnover, it is possible that this chemotactic effect of the protein may be a mechanism for recruitment of these cells to sites of active bone remodeling.
 ...
PMID:Chemotactic activity of the gamma-carboxyglutamic acid containing protein in bone. 660 77

It is axiomatic that a given dose of an antitumor agent will not produce the same effect in 100% of the treated subjects. Numerous explanations regarding the sources of this heterogeneous response to drugs have been offered; however, there is a scarcity of experimental data allowing critical evaluation of the sources of variance. It is possible to study heterogeneous antitumor drug response in experimental, inbred animals. One animal model system, the advanced Ridgway osteogenic sarcoma, exhibits marked variation in its response to maximally tolerated doses of a number of clinically active antitumor agents. To evaluate the role of the host in the variable drug response, the tumor was bilaterally implanted into the flank regions of recipient AKR male mice. Treatment of the advanced tumor (200 mg-1,500 mg) with maximally tolerated doses of vincristine or L-phenylalanine mustard produced marked, but variable antitumor responses. Evaluation of a number of quantal and graded parameters of the chemotherapeutic response suggested that host heterogeneity contributes to variability. The host contribution was more apparent in this experiment model when the agent was noncurative. The underlying biological basis for the host heterogeneity is not known; however, it appears likely that pharmacological, immunological or other differences between the inbred animals account for the heterogeneity. Identification of these factors may be experimentally feasible in this animal model and help in the design of future studies in humans.
 ...
PMID:Role of the host in the variable chemotherapeutic response of advanced Ridgway osteogenic sarcoma. 696 73

We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate-dependent and thus is not corrected by administration of CV. A post-infusion increase in PHE/TYR of 571% after 22 hours in one patient and of 410% after 30 hours in another were associated with marked MTX toxicity. The greatest increase in PHE/TYR seen in a patient who did not experience toxicity was was 249% in 21 hours. Thus, in this group of patients, there appears to be a correlation between evidence of clinical MTX toxicity and the magnitude of the percentage increase in PHE/TYR in the plasma, which indicates inhibition of a liver enzyme and thus reflects the intracellular concentration of MTX.
 ...
PMID:Plasma phenylalanine: tyrosine ratios during high-dose methotrexate-citrovorum "rescue". 698 Oct 54

Comparison is made of the development of resistance to cyclophosphamide (CPA) and L-phenylalanine mustard (L-PAM), of cross-resistance, and chromosome counts, in Walker 256 (W256), rat sarcoma R3 (R3), leukemia L1210, and Ridgway osteogenic sarcoma. For development of resistance the single maximum tolerated doses of CPA or L-PAM were used, each for two sublines in the four tumors. In W256 after only one to five treatment generations, all sublines were resistant, whereas only by generation 10 had R3/CPA, R3/L-PAM, and L1210/CPA reached marked resistance, and L1210/L-PAM reached moderate resistance. All four Ridgway osteogenic sarcoma sublines were essentially still as sensitive as the parent tumor. Long-established resistant sublines from previous studies (greater than 20 treatment generations) were used for cross-resistance, chromosome, and stability studies. All W256-resistant sublines were cross-resistant to CPA, L-PAM, and thiotepa; but the sublines of the other tumors, although showing marked, or in the case of L1210/CPA, complete resistance to their respective inducing agents, retained moderate-to-full sensitivity to the other alkylators. W256/CPA and W256/L-PAM were mainly polyploid (greater than 80% of cells), whereas the other tumors were mainly diploid or near diploid. During 10 to 20 untreated generations the degree of drug resistance remained unchanged in W256 and L1210 lines, but was reduced in R3 and Ridgway osteogenic sarcoma lines. The resistance pattern of W256 appears to be compatible with a simple selection mechanism, whereas those of the three other tumors suggest involvement of multiple determinants. This study suggests that some, but not all, tumors have universal cross-resistance between different types of alkylating agents.
 ...
PMID:Resistance patterns of Walker carcinosarcoma 256 and other rodent tumors to cyclophosphamide and L-phenylalanine mustard. 747 Oct 99

Alkaline phosphatase (ALP) plays an important role in bone mineralization; high levels in differentiated osteoblasts allows their identification easily in vitro. It is generally assumed that the activity of ALP in osteosarcoma-derived cell lines commonly used in studies of bone cell biology is exclusively due to the bone/liver/kidney (BLK) isoenzyme. However, we noted that two human osteosarcoma cell lines, U-2 OS and U-393 OS, predominantly expressed a truncated 1.8 kb mRNA for BLK-ALP. This observation stimulated further investigation upon the ability of ALP to form functional protein. We found that, unlike the BLK-ALP of the Saos-2 osteosarcoma cell line, the activity of U-2 OS ALP was thermostable, unaffected by L-homoarginine and levamisole, but inhibited by L-phenylalanine; these properties are characteristic of the placental and/or placental-like (PL-/PL-like ALP) isoenzymes which are 98% homologous at the amino acid level. In the U-393 OS cell line, which expresses the normal-sized 2.5 kb mRNA in substantially higher levels than that produced by U-2 OS cells, the ALP activity had kinetic properties very similar to that produced by the Saos-2 line for all criteria tested. The HOS osteosarcoma cell line (also known as TE-85), which express the normal-sized 2.5 kb BLK-ALP mRNA only, exhibited ALP activity with kinetic properties of both the BLK and PL-/PL-like isoenzymes. The three test lines, U-2 OS, U-393 OS and HOS, produced PL-/PL-like ALP mRNA and protein constitutively, and levels of these increased in cells treated with 1 microM dexamethasone. However, dexamethasone treatment of cells did not alter the types of ALP isoenzyme expressed. Thus our results show that, like Saos-2 cells, U-393 OS cells produce active BLK-ALP exclusively, whereas U-2 OS cells produce PL-/PL-like ALP only, and the HOS cell line produces both. Our findings have important implications for phenotypic characterization of various human osteosarcoma cell lines, and suggest that the production of PL-/PL-like ALP may be a more common occurrence in osteosarcomas than was originally thought.
 ...
PMID:Constitutive expression of non-bone/liver/kidney alkaline phosphatase in human osteosarcoma cell lines. 899 82


<< Previous 1 2 3 4 Next >>