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

The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates. When (+)-morphine was microinfected into the periaqueductal gray (a site known to mediate morphine analgesia) of drug-naive rats, there was only minimal analgesia, but the hyperresponsivity usually observed after microinfection of (-)-morphine occurred. Also, when (+)-morphine was microinfected into the midbrain reticular formation of drug-naive rats, rotation similar to that following microinjection of (-)-morphine occurred. These behaviors were not blocked by naloxone. Significantly, they typically occur in precipitated abstinence in morphine-dependent rats. These observations suggest that there are at least two classes of receptors, one stereospecific and blocked by naloxone and the other only weakly stereospecific and not blocked by naloxone, and that precipitated abstinence may be due, in part, to a selective blockade of receptors of the former class but not of the latter.
 ...
PMID:Stereospecific and nonstereospecific effects of (+)- and (-)-morphine: evidence for a new class of receptors? 19 42

Two cases of postoperative intussusception (POI) are reported. Both children, 13 and 6 months old, had long and difficult surgery for abdominal neuroblastoma after four courses of chemotherapy. Obstruction of the small intestine occurred on the fifth postoperative day, after feeding had been started again, in the first child, and on the third day in the second one. Surgery revealed a loose ileo-ileal invagination of 10 and 15 cm respectively, which was easily reduced. The postoperative course was uneventful in both cases. Although POI is a classical complication of abdominal surgery, it is often forgotten. In the cases described, the first surgical procedure combined most causative factors for POI: young age, preoperative chemotherapy, prolonged general anaesthesia, extensive retroperitoneal dissection close to components of the neurovegetative system. The use of opioids for postoperative analgesia may be an additional risk factor, as they alter intestinal motility. Epidural analgesia with local anaesthetics should be preferred in such cases.
 ...
PMID:[Postoperative intestinal intussusception in children]. 147 88

Angiotensin II (AII), injected intracerebroventricularly, has been shown to antagonize opioid analgesia. The mechanism for this was obscure. In the neuroblastoma X glioma NG 108-15 hybrid cell line, the K(+)-induced increase in [Ca2+]i can be suppressed by the delta opioid agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) at 0.01-1 microM, an effect completely reversed by the opioid antagonist naloxone. Angiotensin II (AII) at concentrations of 0.1 and 1 microM mobilized free Ca2+ from an intracellular pool, and this effect was antagonized by the AII receptor antagonist saralasin. All (1 microM) had no significant effect on the increase in [Ca2+]i induced by K+, but it blocked the suppressive effect of DPDPE on the K(+)-induced [Ca2+]i increase. The results indicate that mobilization of intracellular calcium may underlie the anti-opioid effect of AII.
 ...
PMID:Mobilization of calcium from intracellular store as a possible mechanism underlying the anti-opioid effect of angiotensin II. 150 24

The cannabinoid receptor that has been pharmacologically characterized for hypothermia, spontaneous activity, analgesia and catalepsy in rodents is the same pharmacological receptor that inhibits adenylate cyclase in vitro. The inhibition of adenylate cyclase by the cannabinoid receptor results from an interaction with Gi, based on the biochemical kinetic properties of the response, the sensitivity to pertussis toxin ADP-ribosylation, and the thermodynamic characteristics of the response. From precedents based on studies of the well-characterized G protein coupled receptors, rhodopsin and the beta-adrenergic receptor, we can predict the tertiary structure of the cannabinoid receptor. Three sites of potential glycosylation are present on the receptor. However, treatment of N18TG2 neuroblastoma cells with tunicamycin to prevent glycosylation of newly synthesized receptors failed to alter cannabinoid-induced inhibition of cyclic AMP accumulation. The cannabinoid response was rapidly desensitized (within 1/2 h). Treatment of cells with tunicamycin failed to alter agonist-induced desensitization processes. These findings can be more veraciously interpreted as we gain a better understanding of the cellular dynamics of the cannabinoid receptor.
 ...
PMID:The cannabinoid receptor: biochemical and cellular properties in neuroblastoma cells. 180 46

Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a covalently bound form. Although there are some discrepancies in the molecular weights of these proteins, it is significant that many investigators have reported a molecular weight of about 60 kd for the receptor, regardless of whether it is of the mu, delta, or kappa type. This finding, together with immunological evidence, suggests that different opioid receptor types may be highly similar, and could conceivably even share a common ligand-binding subunit. Several groups have prepared monoclonal or polyclonal antibodies to purified opioid-binding proteins, which should be useful in mapping the brain regional distribution of the opioid receptors, determining the regions in the peptide involved in ligand binding and association with second messengers, and in determining the relationships among different opioid receptor types. One group has in fact already established an antigenic similarity between a mu-selective opioid-binding protein in mammalian brain, and the delta opioid receptor in NG108-15 neuroblastoma-glioma hybrid cells. One group has reported cloning of the cDNA for a purified opioid-binding protein. Somewhat surprisingly, its predicted amino acid sequence places it in the immunoglobulin superfamily, with strongest homologies to cell-adhesion molecules such as N-CAM. MAG, amalgam and fasciclin II, as well as receptors for peptides such as PDGF and interleukin-6. However, this is consistent with evidence that opioids can modulate cell-cell interactions of monocytes, and provides further support for links between opioids and the immune system. The second messengers mediating opioid actions are still unknown. Opioid agonists affect the activity of adenylate cyclase and ion channels in some tissues, but neither has been shown to mediate opioid analgesia. The sequence homologies of the purified opioid-binding protein OBCAM with tyrosine kinase growth factor receptors suggest additional possibilities for second messengers.
 ...
PMID:Molecular characterization of opioid receptors. 216 Jul 90

The molecular basis of opioid tolerance/dependence has long eluded researchers, but recent advances in receptor regulation have suggested a useful conceptual approach to the problem. In NG108-15 neuroblastoma x glioma hybrid (NG) cells, opioid agonists inhibit adenylate cyclase in a dose-dependent, naloxone-antagonizable fashion. Chronic treatment with opioid agonists results in a series of molecular processes that, in a tolerance-like fashion, counteract this inhibition. These processes include desensitization and down-regulation of receptors and an increase in adenylate cyclase activity. Opioid inhibition of adenylate cyclase and opioid receptor down-regulation also have been observed in the brain. However, most studies have found that the receptors coupled to adenylate cyclase are not of the mu type, which are thought to be the primary mediators of opioid analgesia. Down-regulation has been observed for both mu and delta opioid receptors in the brain. However, in most cases, the time course of down-regulation is not correlated with that for tolerance development, and chronic morphine treatment does not result in down-regulation. Thus, opioid receptors in the brain, like those in NG cells, are subject to dynamic regulation by agonists, which probably has an important role in their function. However, it remains to be established that opioid receptor regulation is the basis of opioid tolerance and dependence.
 ...
PMID:Role of receptor regulation in opioid tolerance mechanisms. 284 42

Conventional methods of treatment having failed in 17 children (aged 9/12 to 16 5/12 years) with incurable solid malignant tumours underwent whole-body hyperthermia (41.8-42.0 degrees C, for 2-3 h), hyperglycaemia (20-25 mmol/l) and polychemotherapy. Five children had neuroblastoma (stage 4), three Wilm's tumour (stage 4 or 5, unfavourable histology), five skeletal sarcoma with metastases, three inoperable malignant liver tumour, and one brainstem tumour of unknown histology. Whole-body hyperthermia was induced by extracorporeal blood warming in an haemodialysis apparatus under neuroleptic analgesia, thermistors measuring the temperature in the oesophagus, rectum, trachea and skin. There were on average four treatment sessions (between one and ten, total 58), a week apart. The result could be assessed in 12 children: one persisting complete remission (19 months-metastasising renal rhabdoid tumour), eight partial or incomplete remissions, and three nonresponders (osteogenic sarcoma; Ewing sarcoma; brainstem tumour). If the risk can be satisfactorily judged the method is useful and of bearable toxicity. The results point to a high antitumour effectiveness of combined hyperthermia and chemotherapy.
 ...
PMID:[Treatment of otherwise incurable tumor diseases in childhood using whole-body hyperthermia and chemotherapy]. 291 80

Caudal epidural administration of morphine was used to provide pain relief to a 5-month-old infant with neuroblastoma and massive abdominal distension. Intermittent injections were performed on 6 occasions over 1 week and resulted in prolonged analgesia (17-20 h) and improved depth of respiration on each occasion. Epidural opioid analgesia should be regarded as technically feasible for relief of cancer pain in patients of all ages.
 ...
PMID:Caudal epidural morphine analgesia for an infant with advanced neuroblastoma: report of a case. 291 2

Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia. A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as "nonclassical" cannabinoid analgetics that conform to this agonist-receptor three-point interaction model. At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor. A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro. Enantio- and stereoselectivity were exhibited by the nonclassical cannabinoid compounds for both the analgetic response and the ability to inhibit adenylate cyclase. The magnitude of the enantioselective response was equal for both the biochemical and physiological endpoints. Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo. A conceptualization of the cannabinoid analgetic receptor is presented.
 ...
PMID:Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model. 335 94

The effects of beta-FNA, a highly selective and irreversible mu opioid receptor antagonist, in altering tumor response in A/Jax mice inoculated with S20Y cells were determined. Inoculation of neuroblastoma cells in control subjects resulted in 100% tumor incidence within 16 days, and mean and median survival times of 36 and 35 days, respectively, following tumor inoculation. Tumor incidence and survival times were comparable to controls for mice given chronic injections of 2 mg/kg and 10 mg/kg beta-FNA every 48 h beginning 2 days after tumor inoculation. Tumor growth was subnormal in the 10 mg/kg beta-FNA group. Both dosages of beta-FNA were found to block morphine-induced analgesia for 48 h. These results suggest that, in and by themselves, mu receptors selectively antagonized by beta-FNA do not play an important role in neuro-oncogenic events.
 ...
PMID:beta-Funaltrexamine (beta-FNA) and neural tumor response in mice. 405 12


1 2 3 4 Next >>