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)

PUFAs such as GLA (n-6) or DHA (n-3) were shown to exert antitumor activity on a human neuroblastoma cell line (NCG) and its VCR-resistant subline (NCG/VCR1, 8.6-fold resistant to VCR) in vitro. The NCG/VCR1 line had markedly decreased intracellular accumulation of [3H]-VCR and an accelerated drug efflux, compared to the NCG. The cytotoxic activity of PUFAs was correlated with the generation of MDA-like products in these cells. When VCR was added simultaneously with GLA or DHA to culture medium, the cytotoxic effect of VCR was about 2-fold enhanced, accompanied by about 1.5-2.0-fold increase of intracellular [3H]-VCR in both cell lines. Fatty acid analysis of membrane phospholipids of the NCG and the NCG/VCR1 cells treated with GLA or DHA showed an increased total PUFAs and SFAs, associated with markedly decreased total MUFAs and an inverted PUFAs/MUFAs ratio. Such phospholipid modification may have altered the membrane physical properties and enhanced the VCR cytotoxicity by increasing intracellular VCR accumulation; however, these PUFAs did not affect the drug efflux sufficiently enough to overcome completely the VCR resistance in the NCG/VCR1 cells. These results indicate that PUFAs partially alleviate the VCR-resistance in human neuroblastoma cells, not directly acting on VCR-resistance mechanism(s).
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PMID:Effects of polyunsaturated fatty acids on vincristine-resistance in human neuroblastoma cells. 188 52

P-glycoprotein is a plasma membrane protein believed to mediate resistance to natural product drugs such as vincristine, Adriamycin, and actinomycin D. To facilitate the study of human P-glycoprotein, monoclonal antibodies (designated HYB-612, HYB-241, and HYB-195) were raised against vincristine-resistant human neuroblastoma (SH-SY5Y/VCR) cells. The antibodies recognize a Mr 180,000 plasma membrane phosphoglycoprotein produced in increased amounts in SH-SY5Y/VCR as well as in vincristine-resistant human neuroepithelioma (MC-IXC/VCR), vinblastine-resistant human leukemia (CEM/VLB100), and actinomycin D- or vincristine-resistant Chinese hamster (DC-3F/AD X and DC-3F/VCRd-5L) cells, as compared to control cells. Radioimmunoprecipitation of proteins in cells metabolically labeled with [35S]methionine, 32Pi, or [3H]glucosamine and Western transfer procedures were used for these studies. Characterization of the HYB-612 or HYB-241 antigen by destructive degradation produced a pattern of results typical of a conformation-dependent protein epitope. HYB-612 recognizes complexes of the Mr 180,000 antigen with an iodinated photoaffinity analogue of vinblastine or with tritiated azidopine. Furthermore, pretreatment of MC-IXC and MC-IXC/VCR cells with HYB-612 or HYB-241 before measurement of tritium-labeled actinomycin D or vincristine uptake increases the amount of drug accumulation in resistant, but not in sensitive, cells. Of importance is the fact that the Mr 180,000 protein is expressed in cells which also contain a Mr 170,000 P-glycoprotein. The relative amounts of the Mr 180,000 and 170,000 species vary from one drug-resistant cell line to another. Evidence that the Mr 180,000 protein is a P-glycoprotein and that there is a conserved complex pattern of resistance-related surface proteins in multidrug-resistant cells is presented in this report.
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PMID:Characterization of monoclonal antibodies recognizing a Mr 180,000 P-glycoprotein: differential expression of the Mr 180,000 and Mr 170,000 P-glycoproteins in multidrug-resistant human tumor cells. 256 79

Results of two consecutive treatment programs for advanced neuroblastoma, including sequential hemibody irradiation, are analyzed and compared. The first treatment program (I-TP) included one single-fraction (7 Gy) irradiation to the upper and lower halves of the body as consolidation of remission achieved by previous chemotherapy with CDDP and VP16. A fractionated technique (2 Gy daily for 4 consecutive days to each hemibody) was used in the second treatment program (II-TP) for children in remission following a combination of CDDP + VP16 and ADM + VCR + CTX. In both treatment programs, chemotherapy was continued according to the same pre-radiation regimen following the two sessions of hemibody irradiation. Overall response rate to pre-radiation chemotherapy was 84% and 60% for I-TP and II-TP, respectively. Thirty-month overall progression-free survival was 0 for I-TP and 20% for II-TP. No treatment-related fatalities occurred. In the subsets of patients who reached complete or good partial remission during the pre-radiation chemotherapeutic phase, 30-month progression-free survival in I-TP and II-TP was 0 and 33%, respectively. The role of fractionated hemibody irradiation in prolonging the progression-free survival can be inferred.
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PMID:Advanced neuroblastoma: results of two treatment programs including sequential hemibody irradiation. 267 76

A 5-day continuous infusion of vincristine (VCR; total dose 4 mg/m2) has been given as part of a high-dose chemoradiotherapy regimen with bone marrow transplantation. Evidence of neurotoxicity, such as weakness, paraesthesia and intestinal hypomotility, was evaluated prospectively in nine patients. Five patients had advanced neuroblastoma and four, relapsed sarcomas, and all had responded to initial conventional-dose therapy. VCR was combined with high-dose melphalan (180 mg/m2) and fractionated total-body irradiation. Plasma concentrations of VCR were measured by radioimmunoassay during and up to 24 h after the infusion. Serum and urine electrolytes and liver function tests were measured during VCR treatment and at regular intervals thereafter. VCR concentration at 1 h ranged from 1.8 to 10.9 (median 6.6) ng/ml, and a steady state was achieved by 13-30 h (median 16 h). Levels above 1 ng/ml were maintained throughout the 5-day period with a mean steady-state concentration of 1.7 ng/ml (range 1.3-2.15). After cessation of the infusion, serum concentrations fell to below 0.25 ng/ml within 24 h. Abdominal pain occurred in one patient, but neither constipation nor ileus was seen. In two patients severe muscle pain occurred in the lower limbs towards the end of the infusion. Significant electrolyte problems did not occur and, in particular, there was no evidence of inappropriate ADH secretion. Transient increases in liver enzymes were common but bilirubin was not elevated during the period of monitoring. This regimen allows a two-fold escalation in the dose of VCR to be administered, producing sustained high serum drug levels without major toxicity.
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PMID:Continuous vincristine infusion as part of a high dose chemoradiotherapy regimen: drug kinetics and toxicity. 304 35

High dose chemo-radiotherapy followed by autologous bone marrow transplantation (ABMT) is known to be an effective treatment in stage IV neuroblastoma (NB). Since October '84, 19 children with NB (12 relapsed or resistant: Group A; 7 in first CR: Group B) received ablative therapy (AT) consisting of VCR (4 mg/mg), L-PAM (140 mg/mg) and fractionated TBI (1000 Rads). Induction strategy at diagnosis or at relapse included high dose Peptichemio, 2-3 cycles of Vincristine-Cyclophosphamide--high dose Platinum and surgery. Bone marrow was harvested after 2 evaluation proved negative by cytomorphology, histology and immunofluorescence. Mononuclear cells (median 6.7 x 10(7)/kg) were cryopreserved and reinfused without purging. At the time of AT in Group A8 children were in CR, 4 had minimal diseases; in Group B 6 were in CR and one in PR. One toxicity-related death occurred on day 7 in a child in first CR; median duration of granulocytopenia 0.5 x 10(9)/l and thrombocytopenia less than 50 x 10(9)/l were 20 days (R: 9-40) and 27 days (R: 11-51) respectively. Persistent immune thrombocytopenia occurred in 4 children. Fever higher tha 38 degrees C developed in all patients: sepsis was documented in 6 patients. Extramedullary toxicity was moderate: GI tract was the most affected. Two out of 5 children who received AT having residual disease achieved CR; relapse or progression of disease occurred in all these patients. Four out of 8 children in second or subsequent CR and 4 out of 5 in first CR are alive and well at 3-12 months (median 7).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Total body irradiation, vincristine in continuous infusion and high-dose melphalan with transplant of autologous bone marrow in the treatment of neuroblastoma]. 330 21

A four-year-old boy with stage IV neuroblastoma was treated using the group study protocol of the Tohoku area for advanced neuroblastoma, consisting of DTIC, CPA, VCR, CDDP and VM-26, as a result of which had obtained complete remission. However, he had severe hemorrhagic cystitis after administration of CPA. He was treated with the usual therapy, but symptoms such as hematuria, pollakiuria and miction pain were not improved. We then tried bladder irrigation with prostaglandin E2. Half a milligram of PGE2 in 100 ml of physiological saline solution was instilled into the bladder and left in situ for 3 hours. The patient was free of symptoms on the day following the therapy. Local therapy with PGE2 thus seems very useful for cyclophosphamide-induced cystitis.
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PMID:[Bladder irrigation with prostaglandin E2 in cyclophosphamide-induced hemorrhagic cystitis]. 342 44

A cooperative multicenter clinical study on cisplatin in children with malignant solid tumors was conducted in seventeen institutions. Of 63 children entered into the study, 18 patients were treated with cisplatin alone, 33 with a VCAP regimen (VCR, CPA, ADM and CDDP) and 12 with other combination regimens. The numbers of evaluable patients were 14, 27 and 7, respectively. Response rates for neuroblastoma were 37.5% (3/8) with cisplatin alone and 79.2% (19/24) for the VCAP regimen. Major adverse effects were gastrointestinal symptoms, bone marrow suppression and renal impairment. Hearing difficulty, electrolyte imbalance and transient elevation of transaminase were also observed. However, these adverse effects were within a tolerable range of severity. The results of this study demonstrate that cisplatin is a useful drug in the treatment of neuroblastoma.
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PMID:[Clinical evaluation of cisplatin in children with malignant solid tumors. Pediatric Cisplatin Study Group]. 367 93

PTC, a mixture of oligopeptides of m-L-sarcholysin, acting primarily as an alkylating agent, was utilized as initial therapy following diagnosis in 80 children with nonlocalized neuroblastoma. Of the 67 evaluable patients (21 Stage III, 41 Stage IV and five Stage IV-S), 51 had measurable lesions allowing to evaluate PTC activity; objective tumor responses to the drug were recorded in 45 of these 51 cases (88.2%); 5/5 Stage III, 37/41 Stage IV, 3/5 Stage IV-S. Complete responses were obtained in seven patients (13.7%), partial responses in 32 (62.7%), objective improvement in six (11.8%). Four patients (7.8%) had either no tumor change, or tumor progression. There have been two early drug-related deaths (3.9%). Stage III and IV patients responding to PTC were then treated by irradiation + VCR, followed by cycles of a combination of ADriamycin, vincristine, and cyclophosphamide. Stage IV-S patients received no further therapy. Thirteen of 21 Stage III (61.9%), five of 41 Stage IV (12.2%) and four of five Stage IV-S (80%) are presently alive from 19-48 months (median, 27 months). PTC is an effective agent in advanced neuroblastoma. However, the results of this report do not indicate that its addition to a "standard" treatment, at least in the schedule adopted in this protocol, has improved the final outcome of children with nonlocalized disease.
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PMID:Effect of peptichemio in nonlocalized neuroblastoma. 708 13

A patient with olfactory neuroblastoma who had bone marrow metastasis at the time of diagnosis is presented. Previous therapy for this disease consisted of surgery and radiation. There is limited information relating to the efficacy of chemotherapy. Our patient was treated with combination chemotherapy (dacarbazine [DTIC-Dome], cyclophosphamide [Cytoxan], doxorubicin hydrochloride [Adriamycin], and vincristine sulfate [Oncovin]) and radiation to the primary site. Objective findings, more than two years after diagnosis, support a good partial response. Although a 50%, five-year survival time has been reported, the five-year cure rate is 18%. This report suggests that the role of combination chemotherapy should be further evaluated in certain patients with olfactory neuroblastoma.
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PMID:Olfactory neuroblastoma. Response to combination chemotherapy. 736 26

The curability of pediatric cancer has been improved to nearly seventy percent. This change has been achieved by refinements in treatment strategy and supportive care. More than seventy percent of patients with ALL can be cured by modern chemo-radiotherapy with reduced late effects. The stratification of the patients by risk factor, introduction of CNS prophylaxis, shortening of the duration of chemotherapy and intensification of the chemotherapy with agents such as HD-MTX have contributed to this remarkable success. Burkitt's lymphoma is a tumor for which the curability has improved from almost zero to ninety percent. With Wilms' tumor, clinical trials have been used to optimally refine the treatment strategy. The NWTS first compared the efficacy of combined VCR and Act-D with the single use of each drug. The difference was significant. The results of the systematic trials were then used to improve the survival rate of patients with Wilms' tumor from twenty to ninety percent and shorten the duration of chemotherapy to six months. On the other hand, tumors remain with which less than half of patients can survive for long. Advanced neuroblastoma and AML are typical such tumors. With these diseases, refinements in the treatment based on evidence derived from clinical trials have been insufficient. Further intensification of the treatment or novel approaches to control tumor growth are warranted for these diseases. In this article, I would like to describe the "standard" therapy for each tumor and the evidence on which improvements in those strategies have been based.
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PMID:[Evidence based chemotherapy for pediatric cancers]. 1070 Aug 90


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