Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plant polysaccharide palyustran inhibited the growth of human lung carcinoma P-1 transplanted to athymic mice by 60% but failed to do so in human rhabdomyosarcoma. Treatment with palyustran was followed by a 2-fold decrease in lympho- and granulocyte levels, selective inhibition of succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activity in tumor cells and--in single cases--metastatic involvement of the liver.
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PMID:[Effects of plant polysaccharide paliustran on the growth of human tumor transplants in athymic mice]. 234 93

Twenty-nine children (median age: 41 months) with advanced solid tumors received, as consolidation therapy, two consecutive courses of high-dose chemotherapy (HDC) followed by mafosfamide-purged autologous marrow transplantation (ABMT) with a 3- to 4-month interval between each course. The malignancies were neuroblastoma (n = 22), Ewing's sarcoma (n = 5) and rhabdomyosarcoma (n = 2). Patients received a preparatory regimen consisting of combined high-dose melphalan before each ABMT, with the exception of five patients who received busulfan and cyclophosphamide before the second ABMT. Prior to HDC, bone marrow sufficient for two transplantations was harvested in remission, treated with mafosfamide (50 micrograms/ml) and cryopreserved. Following incubation with the drug, a consistent inhibition (greater than 99%) of granulocyte and macrophage colony-forming units was observed. Despite the elimination of measurable hematopoietic progenitors, all patients underwent engraftment within a similar period of time after the first and the second ABMT. However, peripheral leukocyte and granulocyte recovery was delayed (median 26 and 28 days, respectively, after the first graft; median 27 and 28 days after the second graft). No difference was observed in the bacterial infections following the first and second ABMT. One patient died after the second transplant with diffuse aspergillosis. Recovery to 50 x 10(9) platelets/l occurred after a median 42 days (range 19-71) after the first ABMT and 43 days (range 14-110) after the second. Two patients died of recurrent disease before attaining a normal platelet level. One patient remained thrombocytopenic and died from visceral failure at day 200. These results demonstrate the feasibility of repeated ABMT with mafosfamide-treated marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemopoietic reconstitution after repeated autologous transplantation with mafosfamide-purged marrow. 279 Mar 32

We studied the effect of total parenteral nutrition on recovery from myelosuppression in patients receiving intensive chemotherapy. Twenty-seven patients (ages 11 to 33 years) with locally recurrent or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma were randomly selected to receive either conventional oral nutrition or total parenteral nutrition concurrently with intensive chemotherapy. The control group (15 patients) received significantly fewer calories (range 380 to 880/m2 per day, median 685 versus range 1,020 to 2,100 median 1,650) and less nitrogen (0-3.7 g/m2 per day, median 1.5 versus range 5.3 to 12.4, median 8.9) than the group receiving total parenteral nutrition (12 patients). Assessment of recovery from myelosuppression was based on the length of time the absolute granulocyte count was below 500/mm3, the length of time the platelet count was below 40,000/mm3, the number of days the platelet count was below 20,000/mm3, and the number of blood transfusions required. There was no statistical difference in any of the parameters evaluated between the group that received total parenteral nutrition and the control group (p less than 0.05); granulocyte and platelet recovery and the difference in transfusion requirements favored the control group with marginal statistical significance (p = 0.05). The frequency of clinical infections was similar in the patients receiving total parenteral nutrition (five of 12) and in those receiving conventional oral nutrition (five of 15). Thus, although total parenteral nutrition could be safely administered in this severely myelosuppressed population, no benefit could be defined in recovery from bone marrow suppression or frequency of clinical infections.
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PMID:The effect of total parenteral nutrition on chemotherapy-induced myelosuppression. A randomized study. 640 92

High-dose multiagent chemotherapy followed by autologous marrow rescue was used in the treatment of 13 patients with Stage III or IV childhood tumors. Encouraging results are being obtained in abdominal lymphoma (1/3 complete remissions (CR); rhabdomyosarcoma (2/4 CR); and retinoblastoma (1/2 CR). In neuroblastoma, the results are disappointing, with only one of four patients in CR; this patient developed a lymphoma associated with Epstein-Barr virus infection. Marrow reconstitution was obtained in 11 patients, with recovery of neutrophils to greater than 0.5 x 10(9)/liter between six and 30 days and platelet recovery to greater than 50 x 10(9)/liter between seven and 38 days. Investigations on the numbers of cells or committed granulocyte precursors ()CFU-c's) infused and parameters of hematologic recovery show poor correlation and suggest that a more accurate and reliable assay for the predictability of cryopreserved marrow to reconstitute marrow function within a reasonable time is necessary. Nonhematologic toxicities of high-dose multiagent chemotherapy are the principal dose-limiting factors.
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PMID:Autologous bone marrow rescue in the treatment of advanced tumors of childhood. 703 50

We have studied the induction of a granulocyte-associated leukocytosis (leukemoid reaction) in C3HA, C57B1/6, and DBA/2 mice by a number of transplantable tumors of different origin. Leukemia L1210, Hepatoma 22, a transplantable mammary carcinoma of spontaneous C3HA origin, and a L929 culture fibroblasts-derived rhabdomyosarcoma, all induced a leukemoid reaction in their specific mouse strain. Melanoma B16 and Lewis lung carcinoma gave no reaction; Adenocarcinoma 755 and Harding-Passey melanoma evoked a leukocytosis but not due to an increase in neutrophils. Some extratumoral factors can influence the hematological response; the intensity of final leukemoid reaction was higher in female mice than in males bearing the same tumor. On the other hand, Ehrlich ascites tumor transplanted in all three inbred mouse strains rendered different levels of leukemoid reaction; response was higher in DBA/2, intermediate in C3HA and lower in C57B1/6.
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PMID:Leukemoid reaction induced by different transplantable tumors in three inbred mouse strains. 707 May 57

Reducing agents such as glutathione (GSH), glutathione ester (GSE), and N-acetylcysteine (NAC) have been shown to suppress the induction of HIV expression in chronically infected cells stimulated by cytokines. We present data which show the effects of the organic thiophosphate WR-151327 on the expression of latent HIV in U1 cells. The chronically infected promonocytic cell line U1 constitutively expresses low levels of HIV that can be increased by 13-phorbol 12-myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), and granulocyte/monocyte colony-stimulating factor (GM-CSF). WR-151327 suppressed, in dose-dependent fashion, the reverse transcriptase (RT) activity induced by TNF-alpha, GM-CSF, and PMA. The maximal decrease in RT activity was 70, 80, and 50%, respectively. Pretreatment with WR-151327 also suppressed the induction of total HIV protein synthesis, as shown by Western blot analysis. In addition, WR-151327 suppressed HIV-LTR-CAT activity in transfected human rhabdomyosarcoma cells (RD). Suppression of HIV expression by WR-151327 was observed in the absence of a cytotoxic or cytostatic effect. Incubation of WR-151327 with human recombinant TNF-alpha for 6 hr at 37 degrees C did not alter the capacity of TNF-alpha to induce the expression of HIV. Our observations further support the hypothesis that reducing agents are important in the control of HIV replication and that the clinical evaluation of WR-151327 may be indicated.
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PMID:Organic thiophosphate WR-151327 suppresses expression of HIV in chronically infected cells. 752 Nov 93

Neutrophils play an important role in the efficacy of photodynamic therapy (PDT). These leukocytes rapidly accumulate into the tumor lesion after PDT and most likely eradicate the remaining attenuated tumor cells. The underlying mechanism of the accumulation of neutrophils at the time of PDT is not known. Therefore, we determined the effect of PDT on the course of mature and immature neutrophils in the circulation of rhabdomyosarcoma-bearing rats and studied the changes in the level of interleukin (IL)-1beta as an important stimulator of the proliferation of precursor cells of the granulocyte lineage in the bone marrow. We found that the effect of PDT on tumor growth was preceded by a rapid and specific increase of the number of mature neutrophils in the peripheral blood as early as 4 h after the start of PDT treatment and reaching maximum values after 8 h. At 24 h, the neutrophil numbers in the PDT-treated rats were still elevated as compared to sham-treated rats. In sham-treated rats, the numbers of blood monocytes and lymphocytes decreased by about 50% after 2 h and returned to their normal levels as soon as 2 h later. In PDT-treated rats, the course of monocyte numbers showed a similar pattern; however, lymphocyte numbers did not reach the normal range until 24 h. The specific increment of neutrophils was preceded by an increase of band neutrophil numbers and elevated serum levels of IL-1beta which were maximal at 2 h after the start of PDT. Pearson correlation analysis showed a significant association between the serum levels of IL-1beta at this time point and the number of band neutrophils at 4 h (R2 = 0.58; P = 0.03) and the number of mature neutrophils at 8 h (R2 = 0.54; P = 0.04). This suggests that PDT evoked an IL-1-dependent increased production rate of neutrophils in the bone marrow. Further investigation showed that the injection of anti-granulocyte colony-stimulating factor (G-CSF) antibodies not only attenuated the increase in neutrophil numbers but also greatly decreased the efficacy of PDT. On this basis, we suppose that an IL-1-induced release of G-CSF by PDT underlies this nonspecific immune reaction to the tumor. Apparently, G-CSF not only stimulates the production rate of neutrophils in the bone marrow but also increases the functional activity of these leukocytes to become indispensable tumor cell killers.
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PMID:Role of interleukin 1 and granulocyte colony-stimulating factor in photofrin-based photodynamic therapy of rat rhabdomyosarcoma tumors. 920 52

The disease-free survival of children with malignant disorders has increased impressively over the last three decades due to better understanding of tumour biology and the resultant improvement in diagnosis and therapy. Children with advanced and relapsed solid tumours, such as brain tumour, alveolar rhabdomyosarcoma, Ewing's sarcoma, or neuroblastoma, have not benefited from this progress. The concept of myeloablative high-dose chemotherapy (HDT) is based on the observation that certain cytostatic drugs have a steep linear dose-response curve, and thus escalating the dose may increase the tumour cell kill. The interest in HDT intensified when autologous stem cells mobilised from the peripheral blood became available, in view of the possibility of increasing the cell dose, which correlates directly with the time period of haematopoietic recovery and thus reduces therapy-associated toxicity. The aim of the study was to evaluate the feasibility of single or double HDT by autologous peripheral blood stem cell transplantation (PBSCT) after each cycle in children, and to obtain pilot data for future prospective clinical trials. 11 children aged between 2.8 and 17.2 years with brain tumours, soft tissue sarcomas, germ-cell tumours and neuroblastomas were analysed over a 2-year-period. 7 of the 11 children are in complete remission 2+ and 24+ months after HDT, 3 died of progressive disease and one child died of therapy-associated complications. The median hospital stay was 29.5 (22-104) days. An absolute neutrophil granulocyte count of 0.5 x 10(9)/l was achieved after a median stay of 11 days and a platelet count of > 20 x 10(9)/l independent of platelet transfusions was achieved after 11 days. Painful stomatitis leading to total parenteral nutrition (9 children) and intravenous morphine therapy (6 children) was the most serious toxicity. Single or double HDT with autologous PBSCT after each cycle is feasible in children and offers basic data for conducting phase III paediatric clinical studies.
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PMID:[Single and double high-dose chemotherapy with autologous stem cell transplantation in children with advanced solid tumors: first experiences]. 1078 56

AC133, a newly discovered antigen on human progenitor cells, demonstrating 5-transmembranous domains is expressed by 30-60% out of all CD34+ cells. Our aim therefore was to investigate the extent of human stem-/progenitor cells expressing AC133 antigen in umbilical cord blood, peripheral blood without or following an application of granulocyte-colony stimulating factor (rhG-CSF). The main task was the investigation of bone marrow aspirates derived from children suffering from newly diagnosed acute leukemias, as well as from patients with a relapse or during a complete remission. The determination of antigen expression was done by application of flow cytometry (FACScan analysis) and the usage of newly developed monoclonal antibodies (AC133/1 and AC133/2; Miltenyi Biotec GmbH) in combination with monoclonal antibody directed against CD34-antigens (HPCA-2; BD). Our studies till now show average percentages in umbilical cord blood derived from 43 newborns about 0.294 +/- 0.165% AC133+ vs. 0.327 +/- 0.156% CD34+ hematopoietic stem-/progenitor cells (HSPC). In peripheral blood from 11 healthy donors we verified up to 0.15% CD34+ as well as AC133+ HSPC's. The concentration of progenitor cells was found to be obviously higher in peripheral blood from children with various diseases (neuroblastoma, rhabdomyosarcoma, ALL/AML) and undergoing application with rhG-CSF in order to be prepared for PBSC-transplantation. In those cases we found up to 3.51% AC133+ cells as well as slightly higher values (3.94%) for CD34 antigens. Additionally we quantified 128 bone marrow (BM) samples for AC133+ and CD34+ cells. In 10 BM samples, derived from patients without any neoplasia, the CD34+ cells were about 0.03% and 1.49%, whereas AC133 values were up to 0.64%. Bone marrow aspirates from 53 children with acute leukemias at time of diagnosis (ALL: n = 41/AML: n = 12) have been immunophenotyped and leukemic blast cells have been proved for AC133- and CD34 antigen expression. 32/41 (78%) of lymphoblastic leukemic cells showed to be positive for CD34 antigen and 24/41 (58%) demonstrated AC133 antigens. Interestingly there were 2 ALL-patients with pathological blast cells positive for AC133 but lacking of any CD34 antigens. 42% (5/12) of investigated AML patients showed CD34+ phenotype, on the other hand there were only 25% (3/12) with AC133+ phenotype. Similar values were found in relapsed patients (n = 18). In BM samples from patients during complete remission (n = 47) we could detect percentages up to 5.55% for CD34 and up to 1.25% for AC133 positive stem-/progenitor cells. Such quite high data may be explained by occasionally application of rhG-CSF therapy. Our results till now lead to the conclusion, that it seems to be useful, to recruit quantification of CD34+ HPSC by additionally detecting AC133 antigens. This new stem cell marker (AC133) may be of great value in case of autologous peripheral blood stem cell transplantation (PBSCT) because it could be an alternative to the usual CD34+ MACS selection system.
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PMID:[Expression of AC133 vs. CD34 in acute childhood leukemias]. 1091 77

Paediatric solid tumours exhibit steep dose-response curves to alkylating agents and are therefore considered candidates for high-dose chemotherapy and autologous stem cell support. There is growing evidence that autologous stem cell grafts from patients with solid tumours are frequently contaminated with live tumour cells. The objective of this study was to perform, in a preclinical purging model, an initial assessment of the safety and efficacy of a two-step purging procedure that combined Merocyanine 540-mediated photodynamic therapy (MC540-PDT) with a brief exposure to the alkyl-lysophospholipid, Edelfosine. Human and murine bone marrow cells and Neuro-2a murine neuroblastoma, SK-N-SH human neuroblastoma, SK-ES-1 and U-2 OS human osteosarcoma, G-401 and SK-NEP-1 human Wilms' tumour, and A-204 human rhabdomyosarcoma cells were exposed to a fixed dose of MC540-PDT followed by a brief incubation with graded concentrations of Edelfosine. Survival was subsequently assessed by in vitro clonal assay or, in the case of CD34-positive haematopoietic stem cells, by an immunohistochemical method. Combination purging with MC540-PDT and Edelfosine depleted all tumour cells by >4 log while preserving at least 15% of murine granulocyte/macrophage progenitors (CFU-GM), 34% of human CFU-GM, and 31% of human CD34-positive cells. The data suggest that combination purging with MC540-PDT and Edelfosine may be useful for the ex vivo purging of autologous stem cell grafts from patients with paediatric solid tumours.
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PMID:Preferential inactivation of paediatric solid tumour cells by sequential exposure to Merocyanine 540-mediated photodynamic therapy and Edelfosine: implications for the ex vivo purging of autologous haematopoietic stem cell grafts. 1263 81


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