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)

Sixty patients consisting of 56 cases with leukemia, 3 with lymphoma and 1 with neuroblastoma were treated with various kinds of hematopoietic stem cell transplantation. The conditioning regimen consisted of mainly cyclophosphamide (CTX) and total body irradiation (TBI) with the addition of 1-3 doses of other antitumor drugs e.g. cytarabine, daunomycin, etoposide, 6-MP etc. The overall incidence of hemorrhagic cystitis in the course of transplantation was 23.3% (14 out of 60 patients). The time of onset of hematuria in 6 of 14 patients was within 1-4 days following high-dose CTX during conditioning and in the remaining 8 cases occurred 10-30 days after transplantation. The duration of hematuria lasted 2-31 days (mean, 4 days). Thirteen patients recovered and one patient died from the complication.
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PMID:[Hemorrhagic cystitis in the course of hematopoietic stem cell transplantation]. 790 67

The effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAGO), the delta opioid receptor agonist, Tyr-D-Pen-Gly-Phe-D-penicillamine (DPDPE) and the kappa-opioid receptor agonist, dynorphin A-(1-13) on the whole-cell K+ currents (IK) of cultured mouse DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells were studied. These opioid ligands all elicited dual effects. Low concentrations (< nM) usually elicited a transient increase in IK (within 1 min), followed by a sustained decrease in IK. In contrast, microM concentrations rapidly elicited a sustained increase in IK. After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained decrease in IK evoked by < nM opioid agonists no longer occurred. Low concentrations then elicited only a sustained increase in IK. On the other hand, after chronic treatment with pertussis toxin (PTX), the usual microM opioid-induced increases in IK no longer occurred and more than half of the cells responded with a sustained decrease of IK to microM as well as nM opioids. The results suggest that mu, delta and kappa opioid receptors are each coupled to K+ channels through CTX-B- and PTX-sensitive transduction systems. Both systems have similar threshold concentrations to opioids. Activation of the CTX-B-sensitive opioid receptor/transduction system resulted in a decrease in K+ conductance of the cell which is generally associated with an increase in neuronal excitability. Activation of the other system resulted in an increase in K+ conductance which will, in general, decrease neuronal excitability. The net change in the IK depends upon which effect predominates. The dominance at different opioid concentrations may depend on the relative efficacies of the coupling of these two systems to K+ channels.
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PMID:Dual regulation by mu, delta and kappa opioid receptor agonists of K+ conductance of DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells. 857 91

Cyclophosphamide (CP) and Ifosfamide (IF) are of great importance in the therapy of neuroblastoma (NB). They are prodrugs which have to be activated by microsomes in order to become active compounds. We established a test system which allowed the activation of CP and IF by liver microsomes in the presence of NB cells. The data from these experiments showed that neuroblastoma cells (SK-N-SH, SK-N-LO and IMR-5) were unable to activate CP and IF, but in the presence of rat liver microsomes considerable cytotoxicity was achieved, similar to those of the preactivated derivatives maphosphamide (MP) and 4-hydroxy-ifosfamide (4-OH-IF). Compared to other compounds the final metabolite acrolein contributes significantly to the cytotoxicity of CP and IF, obviously through significant lowering of the glutathione levels in the cells. The incubation system as described allows the rapid determination of the cytotoxicity of CP and IF in the simultaneous presence of microsomes. The results show great differences in the sensibility of NB cells toCP and IF.
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PMID:Effects of cyclophosphamide and ifosfamide on neuroblastoma cells before and after activation by microsomes. 913 38

Whole-cell patch-clamp recordings were used to study Ba2+ currents through voltage-dependent Ca2+ channels in dorsal root ganglion x mouse neuroblastoma hybrid (F-11) cells. Opioid agonists selective for either mu (Tyr-D-Ala-Gly-Mephe-Gly-ol; DAMGO) or delta (Tyr-D-Pen-Gly-Phe-D-Pen-OH; DPDPE) receptors inhibited high-threshold Ba2+ currents. The inhibition was reversible, naloxone-sensitive, and dose-dependent. The inhibitory effects of both DAMGO and DPDPE were blocked by pretreatment of the cells with pertussis toxin (PTX) as well as by brief exposure to the sulfhydryl alkylating agent, N-ethylmaleimide (NEM). The N-type Ca2+ channel antagonist omega-conotoxin GVIA (omega-CTX GVIA) irreversibly inhibited high threshold Ba2+ currents by 66% and blocked the inhibitory effect of DAMGO or DPDPE. In contrast, the L-type Ca2+ channel blocker nifedipine inhibited high threshold Ba2+ currents by 15% and failed to block the inhibitory effect of DAMGO or DPDPE. These results demonstrate that mu and delta opioid receptors are negatively coupled to N-type Ca2+ channels via PTX- and NEM-sensitive GTP-binding proteins in F-11 cells.
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PMID:Mu and delta opioids but not kappa opioid inhibit voltage-activated Ba2+ currents in neuronal F-11 cell. 935 88

The Bone Marrow Transplantation Program in Belarus was founded in 1992, and in 1993, a Bone Marrow Transplantation Centre was created in Minsk. From February 1994 to April 1996, 19 allogeneic bone marrow, 16 autologous bone marrow and 10 autologous peripheral blood stem cell transplantations were performed. Reasons for transplantation included chronic myeloid leukemia, multiple myeloma, severe aplastic anemia, acute myeloid leukemia, acute lymphoblastic leukemia, progressive myelofibrosis, Hodgkin's disease, non-Hodgkin's lymphoma, and neuroblastoma. Among the patients were two liquidators involved in the Chernobyl cleanup activity, both of whom underwent allogeneic bone marrow transplantation. A variety of ablative preparative regimens were used, and blood progenitor cells were mobilized by treatment with Cytoxan and granulocyte colony-stimulating factor. Therapy-related deaths resulted from graft-versus-host disease, septic shock, veno-occlusive disease bleeding and intestinal pulmonary fibrosis. Because the transplantation procedures were carried out on people who continued to be exposed to low-level irradiation, the post-transplantation period included a conservative strategy for prevention of graft-versus-host disease. There was nothing unusual about the post-transplantation period, although uncertainty about the continuing radiation dose should be taken into account when interpreting these data.
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PMID:The Chernobyl governmental program: two years of experience at the Belarusian Bone Marrow Transplant Centre. 936 16

Many poor-risk neuroblastomas and tumours of the Ewing's sarcoma family (ET) recur despite autologous transplants. Recurrence may be due to tumor cells contained in the BM harvests or PBSC harvests. The objectives of this prospective study were to: (1) determine the incidence and degree of tumor cell contamination in paired BM and PBSC harvests; and (2) determine the efficacy of tumor cell purging by immunomagnetic CD34+ cell selection. 198 samples from 11 consecutive patients with neuroblastoma or Ewing's sarcoma were analyzed. We assayed tumor contamination by RT-PCR assay for PGP 9.5, plus immunohistochemistry for neuroblastoma-specific antigens (the latter in neuroblastoma only). None of these patients had tumor cells detected in their BM by clinical histology immediately before BM or PBSC harvests. However, 82% of PBSC and 89% of backup BM harvests were contaminated with tumor by RT-PCR and/or immunocytochemistry assays. Unselected PBSC and BM harvests contained similar quantities of tumor cells (median, approximately 200000 cells). Cyclophosphamide plus G-CSF mobilization did not affect the incidence or level of contamination in PBSC harvests, as compared to blood obtained before mobilization. Immunomagnetic CD34+ cell selection depleted tumor cells by a median of 3.0 logs for PBSC, and 2.6 logs for BM harvests.
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PMID:Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma. 1045 60

Current methods of detection for fish and shellfish biotoxins in monitoring and research purposes are either labor intensive, expensive, require specialized techniques or all of the above. This paper reports on the development of a fairly sensitive, rapid, and inexpensive assay which detects the presence of compounds that affect the sodium channel. It is based on the principles of the mouse neuroblastoma tissue culture assay for sodium channel specific-biotoxins using red blood cells (RBCs) from the red tilapia (Sarotherodon mossambicus). This assay has the potential to complement the use of live animal bioassay testing for marine toxins. Veratridine, a sodium channel activator and ouabain, an inhibitor of Na(+)/K(+) ATPase, both react with the tilapia RBCs by affecting the permeability of the cell's membrane. Saxitoxin (STX), its analogs, and tetrodotoxin (TTX) can inhibit the action of veratridine and ouabain leaving the cell morphologically normal. By sequencing the addition of veratridine and ouabain, with either the extracted samples, saxitoxin, tetrodotoxin, or ciguatoxin (CTX-a sodium channel activator) to the RBCs a sodium channel antagonist or activator can be detected. Results using pure concentrations of a sodium channel-specific toxin could be detected to inhibit hemolysis at a concentration of 0.3 microg/ml STX, 3.5 microg/ml for neo-STX, 3.0 microg/ml for GTX, and 5.0 microgl for TTX in the presence of ouabain and veratridine. CTX was detected at a concentration of 50 microg/ml. The RBCs from the red tilapia was used due to the fish's ability to osmoregulate its internal environment to survive in both fresh and saltwater. In addition, with growing opposition to live animal testing, this assay has been designed as a non-lethal means of testing for sodium channel affecting marine toxins. No test animals are sacrificed and blood may be drawn from the same fish for continued sample testing.
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PMID:A rapid hemolysis assay for the detection of sodium channel-specific marine toxins. 1111 65

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

Inhibiting Ca(2+) uptake by the sarcoendoplasmic reticular Ca(2+)-ATPase pump (SERCA) causes release of Ca(2+) from the endoplasmic reticulum (ER), increased cytosolic Ca(2+) ([Ca(2+)](cyt)) and depletion of ER Ca(2+) stores. These studies were designed to test the effects of SERCA inhibition on neuronal viability, using as a model the human neuroblastoma cell line, SH-SY5Y. Continuous exposure to the SERCA inhibitor thapsigargin (TG) decreased SH-SY5Y viability to <30% after 48 h exposure, and produced DNA laddering. Two other SERCA inhibitors, BHQ and cyclopiazonic acid CPA, were similarly toxic, although at 1000-fold higher concentrations. BHQ and CPA toxicity was prevented by removing drug within several hours, whereas TG toxicity was essentially irreversible. All three SERCA inhibitors caused an increase in [Ca(2+)](cyt) that was partially blocked by the ryanodine receptor inhibitors, dantrolene and DHBP. Pretreatment with 40 microM dantrolene gave substantial protection against TG- or BHQ-induced cell death but it did not inhibit death from staurosporine, which does not cause release of ER Ca(2+). DHBP (20-100 microM) also gave partial protection against TG toxicity, as did ruthenium red (2 microM), but not ryanodine (10 microM). Inhibition of capacitative Ca(2+) entry with EGTA or LaCl(3) or low extracellular Ca(2+), or chelation of [Ca(2+)](cyt) with BAPTA-AM, failed to inhibit TG toxicity, although they prevented increases in [Ca(2+)](cyt) caused by TG. Taken together, these data suggest that toxicity caused by SERCA inhibition in SH-SY5Y cells is caused by ER Ca(2+) depletion, which triggers an apparent apoptotic pathway.
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PMID:Depletion of intracellular calcium stores is toxic to SH-SY5Y neuronal cells. 1175 Sep 1

Clinical reports and descriptions of chronic fatigue syndrome (CFS) and chronic ciguatera fish poisoning (CCFP) show great similarities in clinical symptomology. These similarities in the literature suggested the exploration of lipids in sera of CFS, CCFP, and other diseases with the membrane immunobead assay (MIA), which is typically used for screening ciguateric ocean fish. Sera from patients with other diseases, including hepatitis B, cancer, and diabetes, were included to assess the degree of specificity involved. Sera were treated with acetone in a ratio of 1 part serum to 4 parts acetone. The suspension was centrifuged, and the acetone layer was evaporated. The residue was weighed and redissolved in 1.0 mL methanol and tested by the MIA, undiluted and titered to 1:160. The undiluted acetone fraction of the 37 normal showed +/- activity to +activity with 16 no titer, 15 with 1:5 titer and two with 1:10 titer, and four with > or =1:40 titers. One hundred fifteen CFS sera showed 1 with 1+ and 114 with 2+ activity in the undiluted samples, 1 with 1:10 titer, 3 with 1:20 titer, 31 with 1:40 titer, 50 with 1:80 titer, and 30 with 160 titer. Thus 95.6% of the samples had > or =1:40 titer. Eight hepatitis B sera samples had > or =1:40 titers. Four CCFP samples had > or =1:40 titers. Three of 16 cancer samples had 1:40 titer. These data are summarized in Fig. 1. As shown in Table 1, a significant increase (P<0.001) in the chronic phase lipids (CPLs) was shown relative to the normal group. A preliminary chemical study in C18 octadecylsilyl columns showed all fractions (100% chloroform, 9:1 chloroform : methanol, 1:1 chloroform : methanol, and 100% methanol) to contain lipids reactive to MAb-CTX with different intensities. Prostaglandins were shown in 100% methanol fraction. Competitive MIA with crude fish ciguatoxin and CFS with synthetic JKLM ciguatoxin epitope suggested similarities in structure with ciguatoxin. This was compatible with the neuroblastoma assay demonstrated in the C(18) column fractions 9:1 and 1:1, chloroform : methanol solvents.
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PMID:Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX. 1278 62


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