Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of overall toxicity was analyzed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF). The dosages of HD-MTX ranged from 50 to 350 mg/kg. Overall toxicity was assessed on the basis of five manifestations of toxicity: stomatitis, dermatitis, myelosuppression, liver dysfunction, and kidney function abnormalities. The great majority (91.4%) of the infusions were well tolerated, but 8.6% were associated with moderate or severe toxicity. Stomatitis and serum glutamic-oxaloacetic transaminase (SGOT) changes were the most frequent postinfusion findings. Three patients died from causes related to MTX toxicity. Dose, age, sex, and number of prior infusions were investigated by logistic regression analysis for prognostic effect on frequency of moderate to severe overall toxicity. Age and number of prior infusions had significant (P less than 0.06) effects on overall toxicity. Patients older than 15 years with greater than 10 prior infusions constituted the "high risk" group with a risk of moderate to severe toxicity 6.3 times that of the younger patients with fewer than 10 infusions.
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PMID:Evaluation of overall toxicity of high-dosage methotrexate regimens. 31 42

Plasma methotrexate (MTX) concentrations at 48 hours were determined for 40 patients with osteosarcoma who received 256 infusions of high-dose methotrexate-citrovorum rescue (HD-MTX-CF) regimen. Five manifestations of toxicity (dermatitis, stomatitis, myelosuppression, liver dysfunction, and kidney dysfunction) were considered in the assessment of the overall toxicity. Logistic regression analysis was applied to study the effect of number of prior infusions, age, and 48-hour MTX plasma level on the risk of moderate or severe overall toxicity. Each factor had a significant effect with P less than 0.08. The predicted incidence of moderate-severe overall toxicity in the high-risk group (48-hour MTX level greater than 1.00 x 10(-6) mol/l., prior infusions greater than 10, age greater than or equal to 15 years) was 33.2% compared to only 2.4% in the "low-risk" group (48-hour MTX level less than or equal to 1.00 x 10(-6) mol/l., prior infusions less than or equal to 10, age less than 15 years). The plasma MTX determination at 48 hours postinfusion was found to be independent of both dose infused and patient's age.
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PMID:Significance of the 48-hour plasma level in high-dose methotrexate regimens. 31 68

CCC/2M, CCC/10Y and CCC/MT-2 cat kidney cells producing Japanese isolates of human T-cell leukemia virus type I (HTLVs) and HOS/PL human osteosarcoma cells producing an American isolate of HTLV were infected with vesicular stomatitis virus (VSV) to prepare VSV pseudotypes bearing envelope antigens of HTLVs. VSV propagated in CCC/2M cells contained plaque-forming fractions that were not neutralized by treatment with anti-VSV serum alone: VSV pseudotypes bearing envelope antigens of HTLV2M and CCC cat endogenous virus were formed by infection of CCC/2M cells with VSV. Japanese HTLV2M, HTLV10Y and HTLVMT-2 and American HTLVPL pseudotypes were neutralized by sera of Japanese, American and British patients with ATL. Each serum, including the serum of the patient from whom HTLV2M or HTLV10Y had been derived, gave similar antibody titers against Japanese and American HTLV pseudotypes. The HTLV pseudotypes were also neutralized by rabbit serum raised against HTLVMT-2. A rabbit antiserum against the C-terminal half of the HTLV env protein produced in E. coli also neutralized Japanese and American HTLV pseudotypes. Thus, VSV pseudotype analyses indicated that envelope antigens of HTLVs represent a single serotype worldwide. The env protein produced in E. coli may be used to raise neutralizing antibody against HTLVs.
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PMID:Human T-cell leukemia virus type I: pseudotype neutralization of Japanese and American isolates with human and rabbit sera. 241 68

Twenty-seven patients with osteosarcoma and measurable metastases were treated with low-dose methotrexate (LDMTX) (80 mg/m2), followed by high-dose methotrexate (HDMTX) (7.5 g/m2) after disease progression in 14 patients. LDMTX was administered on Days 1, 8, and 15; if response or stable disease occurred, it was repeated on Days 29 and 43. If response occurred by Day 57, LDMTX was continued every 2 weeks until disease progression. If stable disease occurred by Day 57, the patient crossed over (optional) to HDMTX. HDMTX was given weekly during the first 3 weeks and continued once every 14 days until disease progression. Twenty-five of the patients were evaluable for response. Three patients (12%) achieved complete remission, with durations of 5, 14, and 34 weeks, respectively. The time to disease progression from the start of treatment was 19, 28, and 42 weeks. Twelve patients (48%) had stable disease, with a median duration of 7.5 weeks (range, 6-20). Ten patients (40%) had disease progression. In general, toxicity with LDMTX was mild. The most frequent toxic effect was stomatitis. Twelve of 14 patients who crossed over to HDMTX were evaluated for response. Six patients had stable disease and six had disease progression. We conclude that the results achieved with LDMTX seem inferior to the results achieved with HDMTX described in the literature.
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PMID:Phase II study of low-dose methotrexate in advanced osteosarcoma followed by escalation after disease progression: a study of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research on Treatment of Cancer. 345 32

Treatment of human fibroblast FS-4 cultures with human type II interferon preparations induced the synthesis of at least four proteins that were similar in size to four of the five proteins induced by type I interferons (Mr 120,000, 88,000, 67,000, and 56,000). However, the Mr 67,000 and 56,000 proteins were induced more strongly by type II than by type I interferon, and a counterpart of a Mr 80,000 protein induced by type I interferons was not noticeably induced by type II interferon preparations. We therefore compared type I and type II interferons for relative antiviral activities against different viruses (vesicular stomatitis, encephalomyocarditis, and vaccinia viruses and reovirus) and for cell growth-inhibitory activities on various cell types. The replication of vesicular stomatitis and encephalomyocarditis viruses was inhibited more strongly by type I interferon, whereas reovirus and vaccinia virus showed greater sensitivity to type II interferon preparations. This indicates that viruses may differ in their sensitivity to human type I and type II interferons and that the antiviral mechanisms induced by type I and type II interferons may have significant differences. The type I and type II interferons may have significant differences. The type I and type II interferons may also differ in their efficacies as antiproliferative agents. Type II interferon preparations at 2.5 units/ml inhibited the incorporatin of [3H]thymidine to a greater extent than did type I interferon at 400 units/ml. (For both type I and type II interferons, the unit of interferon activity was defined as the concentration that decreased the yield of vesicular stomatitis virus by 50% in FS-4 cultures.) Furthermore, whereas type II interferon preparations had a reversible cytostatic effect on normal human fibroblasts at 10 units/ml, the transformed cells tested (HeLa, osteosarcoma, U-amnion) showed extensive cell death, thus indicating that it may have a cytocidal effect on certain tumor cells. It appears that human type II interferon (or a factor present in these preparations) may be a potent antitumor agent.
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PMID:Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents. 616 May 87

Dansylcadaverine, amantadine, and rimantadine, which have been shown to inhibit the endocytosis of alpha 2-macroglobulin, epidermal growth factor, and vesicular stomatitis virus [Schlegel, R., Dickson, R. B., Willingham, M. C. & Pastan, I. (1982) Proc. Natl. Acad. Sci. USA 79, 2291-2295], were found to decrease phosphatidylcholine synthesis, chemotaxis, and internalization of a formylated peptide but to stimulate the incorporation of inositol into phosphatidylinositol in rabbit neutrophils. Dansylcadaverine decreased phosphatidylcholine synthesis by both the CDP-choline and transmethylation pathways and also inhibited the synthesis of phosphatidylethanolamine by the CDP-ethanolamine pathway. Dansylcadaverine had no effect on the phosphocholine, CDP-choline, or S-adenosyl-L-homocysteine pools but increased 2-fold the S-adenosyl-L-methionine pool. These results suggest that dansylcadaverine in some manner inhibited the condensation of CDP-choline with diacylglycerol to form phosphatidylcholine. Dansylcadaverine also inhibited phosphatidylcholine synthesis in human neutrophils, human fibroblasts, chicken embryo fibroblasts, rat hepatocytes, osteosarcoma cells, and neuroblastoma cells. It did not stimulate phosphatidylinositol synthesis in chicken embryo fibroblasts.
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PMID:Inhibitors of endocytosis perturb phospholipid metabolism in rabbit neutrophils and other cells. 657 51

Between January 1993 and December 1996, 21 children with advanced solid tumors were entered in a dose-escalating study of high-dose sequential chemotherapy followed by autologous stem cell transplantation. The diagnoses included neuroblastoma (NB) for 13 patients; Ewing's sarcoma (ES) for six patients and osteosarcoma for two patients. Nine patients received therapy as consolidation for primary metastatic disease, and 12 patients had had previous relapses. Treatment consisted of CY given i.v. at a dose of 7 g/m2 on day 1, followed by G-CSF until myeloid recovery. After 3 weeks of rest, all patients were given thiotepa i.v. on days 22-24. The total dose of thiotepa was 450 mg/m2 in three patients, 600 mg/m2 in six patients, and 750 mg/m2 in 12 patients. Melphalan was given i.v. at a dose of 180 mg/m2 i.v. on day 27 followed by stem cell infusion on day 28. Major toxic reactions included stomatitis, esophagitis, diarrhea and dermatitis. Three patients died of treatment-related complications. Twelve patients have had a relapse. Six patients (five with NB and one with ES) are alive in continuous remission 5-50 months (median 36) after transplantation. The results of this study show that it is feasible to administer high-dose sequential chemotherapy to children with advanced solid tumors.
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PMID:High-dose sequential chemotherapy and autologous stem cell reinfusion in advanced pediatric solid tumors. 946 76

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. Biochemical studies have demonstrated that NS5A interacts in vitro with and inhibits the IFN-induced, RNA-dependent protein kinase, PKR, and that NS5A interacts with at least one other cellular kinase. The present study describes the establishment and characterization of various stable NS5A-expressing human cell lines, and the development of a cell culture-based assay for determining the inherent IFN resistance of clinical NS5A isolates. Human epithelioid (Hela) and osteosarcoma (U2-OS) cell lines were generated that express NS5A under tight regulation by the tetracycline-dependent promoter. Maximal expression of NS5A occurred at 48 hours following the removal of tetracycline from the culture medium. The half-life of NS5A in these cell lines was between 4 to 6 hours. NS5A protein expression was localized cytoplasmically, with a staining pattern consistent with the location of the Golgi apparatus and endoplasmic reticulum. In the majority of cell lines, no obvious phenotypic changes were observed. However, three genotype 1b NS5A-expressing osteosarcoma cell lines exhibited cytopathic effect and severely reduced proliferation as a result of high-level NS5A expression. Full-length NS5A protein isolated from a genotype 1b IFN-nonresponsive patient (NS5A-1b) was capable of rescuing encephalomyocardititis virus replication during IFN challenge up to 40-fold, whereas a full-length NS5A-1a and an interferon sensitivity determining region (ISDR) deletion mutant (NS5A-1a-triangle upISDR) isolated from a genotype 1a IFN-nonresponsive patient showed no rescue activity. The NS5A-1b and NS5A-1a proteins also rescued vesicular stomatitis virus replication during IFN treatment by two- to threefold. These data cummulatively suggest that NS5A expression alone can render cells partially resistant to the effects of IFN against IFN-sensitive viruses, and that in some systems, these effects may be independent of the putative ISDR. A scenario is discussed in which the NS5A protein may employ multiple strategies contributing to IFN resistance during HCV infection.
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PMID:Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication. 1009 74

Enveloped viruses, such as vesicular stomatitis virus (VSV) and Influenza virus, have been widely used in studying epithelial cell polarity. Viral particles of VSV-infected epithelial cells bud from the basolateral membrane, which is in contact with the internal milieu and the blood supply. Influenza-infected cells bud viral particles from the apical surface facing the external milieu. This feature can be utilized in labeling polarized membrane domains. We studied the polarity of mesenchymal osteoblasts using osteosarcoma cell line UMR-108 and endosteal osteoblasts in situ in bone tissue cultures. Immunofluorescence confocal microscopy revealed that the VSV glycoprotein (VSV G) was targeted to the culture medium-facing surface. In endosteal osteoblasts, VSV G protein was found in the surface facing bone marrow and circulation. On the contrary, Influenza virus hemagglutinin (HA) was localized to the bone substrate-facing surface of the UMR-108 cells. Electron microscopy showed that in the cases where the cells were growing as a single layer, VSV particles were budding from the culture medium-facing surface, whereas Influenza viruses budded from the bone substrate-facing surface. When the cells overlapped, this polarity was lost. Cell surface biotinylation revealed that 55% of VSV G protein was biotinylated, whereas Influenza virus HA was only 22% biotinylated. These findings suggest that osteoblasts are polarized at some point of their life cycle. The bone-attaching plasma membrane of osteoblasts is apical, and the circulation or bone marrow-facing plasma membrane is basolateral in nature.
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PMID:Polarity of osteoblasts and osteoblast-like UMR-108 cells. 1045 66

Human immunodeficiency virus type 1 (HIV-1) does not replicate in murine cells. We investigated the basis of this block by infecting a murine NIH 3T3 reporter cell line that stably expressed human CD4, CCR5, and cyclin T1 and contained a transactivatable HIV-1 long terminal repeat (LTR)-green fluorescent protein (GFP) cassette. Although the virus entered efficiently, formed provirus, and was expressed at a level close to that in a highly permissive human cell line, the murine cells did not support M-tropic HIV-1 replication. To determine why the virus failed to replicate, the efficiency of each postentry step in the virus replication cycle was analyzed using vesicular stomatitis virus G pseudotypes. The murine cells supported reverse transcription and integration at levels comparable to those in the human osteosarcoma-derived cell line GHOST.R5, and human cyclin T1 restored provirus expression, consistent with earlier findings of others. The infected murine cells contained nearly as much virion protein as did the human cells but released less than 1/500 the amount of p24(gag) into the culture medium. A small amount of p24(gag) was released and was in the form of fully infectious virus. Electron microscopy suggested that aberrantly assembled virion protein had accumulated in cytoplasmic vesicular structures. Virions assembling at the cell membrane were observed but were rare. The entry of M-tropic JR.FL-pseudotyped reporter virus was moderately reduced in the murine cells, suggesting a minor reduction in coreceptor function. A small reduction in the abundance of full-length viral mRNA transcripts was also noted; however, the major block was at virion assembly. This could have been due to a failure of Gag to target to the cell membrane. This block must be overcome before a murine model for HIV-1 replication can be developed.
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PMID:A block to human immunodeficiency virus type 1 assembly in murine cells. 1072 60


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