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 relative inhibitory potency of prostaglandin A (PGA) and prostaglandin J2 (PGJ2) analogues compared to prostaglandin A1 (PGA1) was determined in a clonogenic assay system. Three human melanoma cell strains (C8146A, C8146C, and C8161), a human melanoma cell line (M1RW5) and a human neuroblastoma cell line (IMR-32) were used. Prostaglandin analogues were screened in the clonogenic assay system and the dose effect curves were analyzed by linear regression utilizing the median effect relationship. The computer-generated 50% and 95% inhibitory doses showed that 15-deoxy-16-hydroxyl-16-vinyl-prostaglandin A2 (DHV-PGA2) was from two- to three-fold more active than PGA1 in inhibiting the clonogenic growth of human melanoma cells. Based on the 50% inhibitory dose, PGJ2 and its analogues were from two to five times more potent than PGA1. The delta 12- and delta 12,14-PGJ2 were the most potent of the prostaglandins tested. However, the 95% inhibitory dose for prostaglandin D2 (PGD2), PGJ2 and its analogues against neuroblastoma did not show any enhancement in activity in comparison to PGA1, suggesting that some tumor specificity in the activity of these analogues may be signified by the neuroblastoma data. Prostaglandins which contained a fluoride substitution at position 11 were also tested for activity. As we previously observed with other analogues which did not contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring, 9 beta, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid and 9 alpha, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid did not inhibit the clonogenic growth of human melanoma cells. Administration s.c. to established human melanoma tumors growing in athymic nude mice caused a significant growth inhibition. The treatment schedules ranged from 1 to 8 days. Injection s.c. of PGA1 at a dose of 40 mg/kg/day resulted in a 20% suppression in tumor growth. Higher doses (100 and 200 mg/kg/day) effected an 80% reduction in tumor growth. The higher doses were associated with reversible toxicities, diarrhea and skin inflammation. Administration of DHV-PGA2 at a dose of 20 mg/kg/day resulted in 40% reduction in tumor growth. The increased in vivo potency of DHV-PGA2 corresponds to the results obtained in the clonogenic assay system.
 ...
PMID:Inhibition of human melanoma growth by prostaglandin A, D, and J analogues. 369 5

The antitumor effect of combined use of cis-diamminedichloroplatinum(II) (CDDP) and verapamil, a calcium influx blocker, was examined in neuroblastoma transplanted to BALB/c athymic mice. The response of the tumor to CDDP was related to the dose administered. Regression of the tumor was observed when CDDP was administered at 4.2 mg/kg/injection. The retardation of tumor growth was observed in the group to which CDDP was administered at 2.1 mg/kg/injection. When verapamil was administered with CDDP, regression of the tumor was observed in the group treated with CDDP at 2.1 mg/kg/injection, and the retardation of tumor growth was observed in the group treated with CDDP at 1.4 mg/kg/injection. These results indicate that verapamil enhances the antitumor effect of CDDP against transplanted neuroblastoma in BALB/c athymic mice.
 ...
PMID:Verapamil enhancement of antitumor effect of cis-diamminedichloroplatinum(II) in nude mouse-grown human neuroblastoma. 379 Dec 10

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, an essential precursor for isoprenoid compounds in mammalian cells. Recent studies have shown that mevinolin, a competitive inhibitor of the reductase, inhibits cell proliferation and induces differentiation in cultured C1300 (Neuro-2A) murine neuroblastoma cells. We now report that mevinolin can inhibit neuroblastoma growth in vivo. The specific activity of HMG-CoA reductase in subcutaneous neuroblastomas increased more than 20-fold between the fifth and eighth days after tumor inoculation, and remained elevated for the remainder of the tumor lifetime in mice. The increase in reductase activity was correlated with a marked increase in tumor DNA content and exponential increase in tumor weight. Using an in vitro assay to monitor the ability of mouse serum to suppress sterol synthesis, we determined that mevinolin was inactivated or cleared from the circulation within 3-6 h after a single subcutaneous injection. However, by using subcutaneous osmotic pumps to deliver a constant infusion of mevinolin, we were able to maintain adequate blood levels of the drug for 7 d. Mevinolin (5 mg/kg per h) suppressed tumor growth (wet weight) significantly when treatment was carried out between day 1 and day 8 or between day 5 and day 12 after tumor inoculation. Histopathological examination of tumors from mevinolin-treated mice revealed few or no mitotic figures and marked cellular degeneration. Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo. The data suggest that, in addition to their demonstrated utility as cholesterol-lowering drugs, competitive inhibitors of HMG-CoA reductase may have considerable potential as novel antineoplastic agents.
 ...
PMID:Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. 385 Sep 4

Patients with disseminated neuroblastoma are considered a poor-risk category, hence, our approach towards their treatment should be reconsidered in terms of the unique clinical and biological characteristics of neuroblastoma tumor growth. To this end, we have devised a treatment program consisting of surgery, and a schedule of sequentially escalating doses of cyclophosphamide combined with other drugs until a minimal disease status is obtained. When this is achieved, the patient is treated with maximal therapy, i.e., total body irradiation, high-dose L-phenylalanine mustard and dianhydrogalactitol followed by reconstitution with an autologous bone marrow graft. Details of this program include problems associated with evaluation of response, i.e., evaluation of risk, determination of minimal tumor burden, avoidance of toxicity, and compensation for supportive measures during maximal therapy. Additional problems of purging bone marrow of tumor cells are considered.
 ...
PMID:Autologous bone marrow transplantation. A maximal therapy design for disseminated neuroblastoma. 389

In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on tumor cell proliferation in vitro. When neuroblastoma cells (SK-N-SH) in culture were treated with 12-HETE for 18 hr, incorporation of [3H]thymidine was inhibited up to 64% at concentrations from 20 to 50 microM. Under the same conditions, 15-HETE resulted in inhibition of up to 46%, while arachidonic acid had no apparent effect. When evaluated in the presence of serum, 12-HETE at a concentration of 120 microM produced a 20.6 +/- 2.8% (S.E.) inhibition of the increase in total DNA content over 48 hr, while 15-HETE at this concentration produced a 16.5 +/- 5.3% inhibition. We conclude that 12-HETE, the product of platelet lipoxygenase, and 15-HETE, a product of neutrophil and lymphocyte lipoxygenases, can inhibit human neuroblastoma cell growth in vitro and may play a role in the effect of cyclooxygenase inhibitors on tumor growth in vivo.
 ...
PMID:Inhibition of human malignant neuroblastoma cell DNA synthesis by lipoxygenase metabolites of arachidonic acid. 391 50

The influence which malnutrition plays on the host-tumor relationship is controversial because of the disparity of human and rodent tumors, a critical difference being the minimal immunogenicity of human tumors and the variable antigenicity of rodent tumors. The hypothesis we tested is that the influence of malnutrition on tumor growth is a result of the immunogenicity of the host's tumor. C-1300 neuroblastoma (NB) is an immunogenic tumor by in vivo and in vitro assessment while the histologically identical TBJ-NB clone is non-immunizing. Isogeneic A/J mice were malnourished with 2.5% protein chow and were inoculated with C-1300-NB or TBJ-NB; either serial tumor volumes were assessed by three-dimensional measurement or animals were serially killed and tumor weight/carcass weight ratios (TW/CW) were calculated. Non-immunogenic TBJ-NB grew more rapidly than C-1300-NB in both control and malnourished groups, but there was no difference in either tumor size or TW/CW ratios between the two TBJ-NB nutritional groups. Contrasting with these data were immunogenic C-1300-NB in that the tumor grew significantly better in malnourished mice (tumor volume p less than 0.05 day 12 and 14; TW/CW p less than 0.026 by day 21). Prior whole-body irradiation abrogated this difference. These data demonstrate that for tumors differing only in antigenicity the influence of malnutrition is on that tumor which induces an immunologic antitumor response.
 ...
PMID:Tumor immunogenicity--the prime determinant of the nutritional influence on the host-tumor relationship. 394 43

Improving the prognosis of advanced neuroblastoma remains an important yet unachieved goal of pediatric oncology, a fact which may be related to an insufficient analysis of the role played by cytoreductive surgery. Utilizing strain A mice bearing C-1300 syngeneic neuroblastoma, tumor biology and host immunocompetence were studied after cytoreduction surgery and adjuvant chemotherapy. Cell kinetic analysis in the residual tumor demonstrated an increase of the proliferative fraction 18 to 42 h after operation, but the same peak proliferation was delayed in bone marrow cells to 24 to 96 h. The potential for drug distribution to the tumor after cytoreduction surgery was assessed by injecting Na251CrO4 and measuring tumor uptake. There were two significant (P less than 0.05) peaks of activity at 6 h and 3 days, suggesting local edema and neovascularity, respectively. Injection of both cell cycle specific and nonspecific adjuvant chemotherapeutic agents in a dosage of one-fourth of their 50% lethal dose at 24 or 72 h following surgical cytoreduction did not induce any antitumor activity at either injection time. However, when cyclophosphamide was given in this dose, the C-1300 tumor growth was impaired, an effect which was largely abrogated by first subjecting the tumor bearer to thymectomy and irradiation. The transfer of spleen cells from adjuvant cyclophosphamide-treated mice to tumor-inoculated normal mice significantly delayed tumor appearance when comparison was made with animals treated by operation alone, and such recipients also exhibited a more prolonged survival. These data suggest that the antitumor activity of cyclophosphamide following cytoreduction surgery of C-1300 neuroblastoma is mediated by both pharmacological and immunological mechanisms.
 ...
PMID:Rational selection of adjuvant chemotherapy after cytoreduction surgery for murine neuroblastoma. 401 35

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.
 ...
PMID:Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR. 403 75

Dopamine-beta-hydroxylase activity is present in mouse neuroblastoma C-1300 tumors. The activity is proportional to the weight of the tumor. Serum activity is markedly increased in mice that bear the tumors. Treatment of mice with 5-bromodeoxyuridine causes marked inhibition of tumor growth and decrease of dopamine-beta-hydroxylase activity in the serum. The histochemical studies reveal that 1-5% of the cells in mouse C-1300 neuroblastoma tumors contain catecholamines and that catecholamine-containing processes terminate mainly around blood vessels of the tumor. Dopamine-beta-hydroxylase is present in clonal neuroblastoma cell lines. The cell line with the greater tendency to form axon-like processes has a higher activity of this enzyme.
 ...
PMID:Dopamine- -hydroxylase activity in mouse neuroblastoma tumors and in cell cultures. 450 66

Three murine tumor models, neuroblastoma CL 300, renal cell adenocarcinoma, and Wistar/Furth Wilms' tumor were evaluated for long-term storage in a cryopreservation system. Several transfer generations were observed in all tumor groups. Percent of tumor take poststorage, rate of tumor growth postimplantation and percent of metastatic development were calculated. Tumor take ranged from 5 to 100% poststorage and implant. Tumor growth was noted to require more days with stored tumor than with tumors implanted directly from donor to recipient. Tumor weights were comparable. Metastatic growth was observed in all transfer groups implanted with renal cell adenocarcinoma. Metastatic growth was not observed in all Wistar/Furth Wilms' transfer groups nor in all the neuroblastoma CL 300 transfer groups. This cryopreservation system can be utilized for storing tumor cells with up to 100% recovery of the tumor cell growth.
 ...
PMID:Growth characteristics of murine tumors: neuroblastoma, renal cell adenocarcinoma, Wistar/Furth Wilms' after storage in a cryopreservation system. 608 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>