Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews current approaches to the use of ifosfamide/mesna alone or in combination with other agents or modalities in the treatment of pediatric malignancies. Included are data from current or recently completed studies conducted by major pediatric oncology cooperative groups and large individual oncology centers for patients with newly diagnosed or recurrent tumors. Sarcomas, neuroblastoma, lymphomas, recurrent solid tumors, brain tumors, and acute lymphoblastic leukemia are discussed. Randomized trials to determine the relative efficacy of ifosfamide and cyclophosphamide in various childhood malignancies are under way. The long-term consequences of ifosfamide in survivors of childhood cancer, in terms of development of bladder cancer or other malignancies thought to be associated with alkylating agents, are not known, and will only be determined through follow-up studies of adult survivors. Ifosfamide's future role in pediatric oncology will depend on evaluation of its therapeutic benefits against long-term toxicity.
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PMID:Current studies of ifosfamide for pediatric solid tumors and leukemia in the United States. 148 74

The positron-emitting glucose analogue 18F-2-fluoro-2-deoxy-d-glucose (FDG) was evaluated for its accretion into the following subcutaneous human tumor xenografts in nude mice: B-cell lymphoma (Namalwa or Raji), ovarian carcinoma (HTB77), colon cancer (SW948), choriocarcinoma (BEWO), bladder cancer (UM-UC-2), renal cell carcinoma (UM-RC-3), neuroblastoma (Mey), melanoma (HTB63), and small cell lung carcinoma (NCI69). Two hours postinjection, tumor uptakes ranged from 0.027 (colon cancer) to 0.125% kg injected dose/g (melanoma); and was greater than 0.085 in the Namalwa lymphomas and the renal cell carcinomas. Tumor-blood ratios of up to 23:1 were seen 2 hours postinjection (melanoma) with a mean tumor-blood ratio for all tumors of 12.3 +/- 1.8. Uptake in the other tumors was intermediate. When evaluated, tumor uptake was slightly greater at 1 than at 2 hours postinjection, although target-background ratios were generally higher at 2 hours postinjection. This compound, FDG, may have broad applicability as a tracer for positron-emission tomographic imaging of many human malignancies.
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PMID:18F-2-deoxy-2-fluoro-D-glucose uptake into human tumor xenografts. Feasibility studies for cancer imaging with positron-emission tomography. 200 43

Bleomycin (Blenoxane) and cisplatin (Platinol) are two anticancer drugs with activity for head and neck tumors. Introduced into clinical use in the past ten years, bleomycin is used primarily in the chemotherapy of squamous cell carcinomas, lymphomas, and testicular carcinoma, while cisplatin is effective against testicular and ovarian carcinoma, head and neck cancer, bladder cancer, and neuroblastoma. Bleomycin is rapidly excreted renally (T 1/2 beta = 2-4 hr) although enzymatic inactivation also occurs in many tissues. Cisplatin is nonenzymatically converted to highly protein-bound metabolites, which then undergo renal elimination, but total body clearance occurs much more slowly than with bleomycin (T 1/2 beta = 40-50 hr). Both agents have acute and chronic toxicities; the acute toxicities are generally reversible but cause a great deal of patient discomfort, while the chronic toxicities are often irreversible and dose-limiting. For bleomycin, the acute toxicities are mucocutaneous and pyretic, while severe nausea and vomiting represent the major acute toxicities of cisplatin therapy. Cumulative dose-related pulmonary toxicity is the most serious chronic toxicity of bleomycin. The clinical, radiographic, and pathologic presentations are nonspecific, although identification of high-risk patients may be possible with serial pulmonary function tests. Cumulative nephrotoxicity occurs with cisplatin use and its incidence and severity can be reduced by maintaining adequate hydration and diuresis during and following administration of the drug.
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PMID:Clinical pharmacology of bleomycin and cisplatin. 617 47

Bleomycin (Blenoxane) and cisplatin (Platinol) are two anticancer drugs, with activity for head and neck tumors, that were introduced into clinical use in the past ten years. Bleomycin is used primarily in the chemotherapy of squamous cell carcinomas, lymphomas, and testicular carcinoma, while cisplatin possesses significant activity against testicular and ovarian carcinoma, head and neck cancer, bladder cancer, and neuroblastoma. Bleomycin is rapidly excreted renally (terminal phase half-life = 2-4 h), although enzymatic inactivation also occurs in many tissues. Cisplatin is nonenzymatically converted to highly protein bound metabolites, which then undergo renal elimination, but total body clearance occurs much more slowly than with bleomycin (terminal phase half-life = 40-50 h). Both agents have acute and chronic toxicities; the acute toxicities are generally reversible but cause a great deal of patient discomfort, while the chronic toxicities are often irreversible and dose-limiting. For bleomycin, the acute toxicities are mucocutaneous are pyretic; severe nausea and vomiting represents the major acute toxicity of cisplatin therapy. Cumulative dose-related pulmonary toxicity is the most serious chronic toxicity of bleomycin. The clinical, radiographic, and pathologic presentations are nonspecific, although identification of high risk patients may be possible with serial pulmonary function tests. Cumulative nephrotoxicity occurs with cisplatin use, and its incidence and severity can be reduced by maintaining adequate hydration and diuresis during and following administration of the drug.
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PMID:Clinical pharmacology of bleomycin and cisplatin. 617 75

A significant activity of VM 26 in solid tumors has been established in brain tumors, bladder cancer, and neuroblastoma. Preliminary favorable results in breast cancer stimulated a phase II study at our institution to define the activity of VM 26 in patients with advanced, homogeneously pretreated breast cancer.
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PMID:Phase II study of VM 26 in extensively pretreated breast cancer. 650 65

R 1881 binding receptor and DHT concentrations in human prostatic cytosol were assayed in surgically removed prostatic tissues of benign prostatic hyperplasia (BPH) and of the normal prostate. The normal prostates were obtained from totally cystectomized male patients with bladder cancer. Cytosols were incubated with 0.25--8.0 nM (6 points) of 3H-R 1881 in the presence or absence of excess radioinert R 1881 at 4 degrees C for 20 hours, thereafter treated with 0.5% dextran coated charcoal. Specific bindings were analysed in the form of scatchard plot analysis. Cytosol DHT levels were determined by radioimmunoassay reported previously. Steroid specificity studies revealed that R 1881 binding receptor was inhibited not only by androgens but also by progesterone, however, an addition of 1000 fold excess triamcinolone acetonide (TCA) reduced the inhibition by progesterone. As R 1881-receptor complex was eluted at the void volume of sephacryl S-200 chromatography, the receptor was considered to be 8-9S protein. Cytosol DHT levels were 35.5 +/- 13.6 pg/mg cytosol protein in BPH and 18.9 +/- 7.1 pg/mg protein in the normal prostates, showing a significantly higher value in the former (p less than 0.01). Kd and NBS of R 1881 receptor in BPH were 0.73 +/- 0.21 nM and 30.1 +/- 9.0 fmol/mg cytosol protein and those in normal prostate were 0.68 +/- 0.28 nM, 10.2 +/- 4.2 fmol/mg protein, respectively. NBS were also higher in BPH compared to the normal prostate (p less than 0.001). Moreover, DHT levels (y) and NBS (x) showed a significant correlation (y = 0.631 X + 15.764, r = 0.506).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[R 1881 binding receptor and DHT concentrations in prostatic cytosol]. 668 63

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Experimental radioimmunotherapy. 849 64

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.
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PMID:Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates. 925 48

Cyclophosphamide is a known risk factor for the development of bladder cancer. We report 3 cases of cyclophosphamide-induced bladder carcinoma in 2 individuals treated for Wegener's granulomatosis and in 1 patient with neuroblastoma. Included is a review of the literature on the relative risk of cyclophosphamide therapy, the mechanisms by which the drug induces bladder cancer, and suggestions on how to minimize the deleterious effects of the drug. We conclude that cyclophosphamide should be used in the lowest possible dose and that patients receiving more than 20 g of the drug should undergo routine urinalysis for microscopic hematuria every 3-6 months for up to 11 years after the treatment has been discontinued. Dosages as small as 600 mg in the pediatric population may warrant lifelong monitoring.
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PMID:Cyclophosphamide-induced bladder cancer. 1117 99

The cytotoxicities of 11 lupane series triterpenes against 3 human leukemias, 2 melanomas, 2 neuroblastomas and normal fibroblast cells were examined. Lupane triterpenes with a carbonyl group at C-17 (7-11) showed inhibitory effects on leukemia, melanoma and neuroblastoma cell growth. Lup-28-al-20(29)-en-3-one (8) markedly inhibited the cell growth of 3 leukemias to a greater extent than the other human cancers and normal lung fibroblast cells. The cytotoxicity profiles of 8 against human cancer cells showed that its cytotoxic effect against 3 lung cancer cell lines was strong and the cytotoxic effects against osteosarcoma, breast cancer and urinary bladder cancer cells were very weak. The morphological observations of leukemia nuclei and the gel electrophoresis analysis of DNA extracted from 8-treated leukemia cells revealed that 8 induced leukemia cell apoptosis. Furthermore, we investigated the cytotoxic effects of 8 on adriamycin (ADM)- and vincristine (VCR)-resistant K562 (K562/ADM and K562/VCR) cells. K562/ADM and K562/VCR cells showed greater resistance toward ADM and VCR when compared to parent K562 cells. However, 8 inhibited the drug-resistant K562 cell growth to the same extent as K562 cells by the induction of apoptosis.
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PMID:Anti-leukemia activities of Lup-28-al-20(29)-en-3-one, a lupane triterpene. 1269 74


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