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)

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

FK 973, a new substituted dihydrobenzoxazine, was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of streptomyces sandaensis No. 6897. FK 973 had cytotoxic effects against in vitro cultured human and murine glioma cells. The concentration of FK 973 required to inhibit cell growth by 50% was 0.06-5 micrograms/ml, after 2-day exposure of this drug against human glioblastoma (ONS-6, 12, 23, and ONS-12/ACNU), human medulloblastoma (ONS-76, 81), human neuroblastoma (ST), and murine glioblastoma (RSV-M glioma). FK 973 showed antitumor efficacy in the meningeal gliomatosis models by RSV-M glioma cells. The median survival time (MST) of models treated by FK 973 (i.t.) was 30 days. However, the MST of control group was 23 days. In the in vitro neurotoxicity test, FK 973 proved to be slightly more toxic than ACNU and MTX, but it had no crucial problems, compared with ADM.
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PMID:[Antitumor efficacy of FK 973 on malignant glioma cells]. 275 17

Five patients with advanced neuroblastoma were treated with the protocol of the Welfare Ministry used by the Sawaguchi group. This protocol consists of cyclophosphamide (CPM), vincristine (VCR), 4'-O-tetrahydropyranyladriamycin (THP-ADM) and cisplatinum (CDDP). Two patients treated with this protocol as the first therapy obtained partial remission. Two patients who had obtained complete remission before the treatment with this protocol remained in complete remission after the treatment. One patient who had shown poor response to the therapy given before treatment with this protocol also showed poor response to the protocol. The most significant side effect with this protocol was myelosuppression, the severity of which was closely related to the dose of THP-ADM. Damage to the liver, kidney and heart was not very significant. We advocate that patients with advanced neuroblastoma can obtain complete remission with the aid of surgery and radiotherapy, etc., if they are treated with the present protocol as the first therapy.
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PMID:[Therapy of advanced neuroblastoma by the protocol of the Welfare Ministry used by the Sawaguchi Group]. 334 28

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

Inhibition of human [125I]calcitonin gene-related peptide-I ([125I]hCGRP-I) binding by human adrenomedullin (hADM), its N-terminal truncated fragments, CGRP and amylin, and cyclic AMP accumulation were examined in the human neuroblastoma cell line SK-N-MC. Binding of [125I]hCGRP-I (125 pM) was inhibited by hCGRP-I, hADM(1-52), hADM(13-52), and human amylin with IC50 of 0.32 +/- 0.06, 2.11 +/- 0.26, 3.45 +/- 0.54, and 68.8 +/- 6.6 nM, respectively. hCGRP-I(8-37) and hADM(22-52), which lack the N-terminal ring structure, inhibited [125I]hCGRP-I binding with IC50 of 2.35 +/- 0.45 and > 1000 nM. hCGRP-I, hADM(1-52), hADM(13-52) and human amylin stimulated cAMP accumulation with EC50 of 0.40 +/- 0.05, 18.1 +/- 2.6, 51.3 +/- 9.0 and 925 +/- 159 nM, respectively. hCGRP-I(8-37) (100 nM) antagonized hCGRP-I and hADM(1-52) stimulated cAMP production with the same Ki of 16.6 +/- 1.2 and 16.8 +/- 1.1 nM. In conclusion, human ADM, which is more distantly related to CGRP than amylin, interacts more potently with the CGRP receptor in SK-N-MC cells than amylin. The N-terminal ring structure of hADM, unlike that of hCGRP, is essential for binding to the CGRP receptor. Coupling of hADM binding to cAMP stimulation is less efficient than for hCGRP-I and is reduced by deletion of the unique 12 amino acid sequence of hADM N-terminal to the ring structure.
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PMID:Adrenomedullin and calcitonin gene-related peptide interact with the same receptor in cultured human neuroblastoma SK-N-MC cells. 765 94

It was found a solid tumour of 24 x 28 x 31 mm size above the right kidney with ultrasound screening in a three days old newborn. After three days appeared cystic areas inside the tumour, so it was thought to adrenal haemorrhage. The tumour didn't decrease during two months and metastases developed in the liver. The urinary VMA level was normal, the HVA elevated. The MIBG scintigraphy was first negative, after a month pathognostic. The primer tumour and metastases disappeared after cyclophosphamid and Adriablastin treatment. The adrenal neuroblastoma can imitate the adrenal apoplexy, so it's important to control all neonatal adrenal haemorrhage until their disappearance.
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PMID:[Neonatal neuroblastoma detected by ultrasonic screening]. 823 51

Ganglioside GM2 is expressed on the surface of neuroblastoma and glioblastoma cells, and may also be detected on lung cancer cells. We reported previously that anti-ganglioside GM2 antibody exhibited strong in vitro anti-tumor activity against adriamycin-resistant cancer cells, which overexpressed ganglioside GM2. In the present study, we examined the in vivo anti-tumor effect of the chimeric anti-ganglioside GM2 antibody, KM966, against human lung and breast carcinoma cells, SBC-3 and MCF-7, and respective adriamycin-resistant clones, SBC-3/ADM and AdrR MCF-7 in BALB/c nu/nu mice. Ratios of tumor volume (T/C) between KM966-treated group and control group were 0.01 for SBC-3, 0.00 for SBC-3/ADM, 0.85 for MCF-7 and 0.34 for AdrR MCF-7 cells, respectively. Nude mice, which were pretreated with anti-asialo GM1 antibody to remove natural killer cells, were transplanted with 4 x 10(7) of SBC-3 and SBC-3/ADM subcutaneously. Seven days later, when tumors had grown to a diameter of over 8 mm, mice began to receive intravenous treatment of 120 microgram/mouse KM966 daily. Fourteen daily treatments induced regression to less than 4-mm diameter in 4/5 SBC-3 tumors and 5/5 of SBC-3/ADM tumors. All SBC-3/ADM tumors disappeared completely, suggesting that KM966 exerts a strong in vivo anti-tumor effect on ganglioside GM2-expressing cancer cells. In KM966-treated mice, the surface of the tumor cells stained positive with anti-human IgG. In addition, numerous leukocytes had infiltrated into the tumor mass. Antibody-dependent cell-mediated cytotoxicity (ADCC) of KM966 against tumor cells was examined in vitro by (51)Cr-release assay and revealed that KM966 induces ADCC activity against ganglioside GM2-expressing tumors. Our results suggest that immunotherapy using KM966 may be useful for the treatment of ganglioside GM2-expressing solid tumors.
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PMID:Effect of a chimeric anti-ganglioside GM2 antibody on ganglioside GM2-expressing human solid tumors in vivo. 1041 77

One of the major problems in cancer chemotherapy are the severe side effects that limit the dose of the anticancer drugs because of their unselectivity for tumor versus normal cells. In the present work, we show that coupling of anthracyclines to peptides is a promising approach to obtain selectivity. The peptide-drug conjugate was designed to bind to specific receptors expressed on the tumor cells with subsequent internalization of the ligand-receptor complex. Neuropeptide Y (NPY), a 36-amino acid peptide of the pancreatic polypeptide family, was chosen as model peptide because NPY receptors are overexpressed in a number of neuroblastoma tumors and the thereof derived cell lines. Daunorubicin and doxorubicin, two widely used antineoplastic agents in tumor therapy, were covalently linked to NPY via two spacers that differ in stability: an acid-sensitive hydrazone bond at the 13-keto position of daunorubicin and a stable amide bond at the 3'-amino position of daunorubicin and doxorubicin. Receptor binding of these three conjugates ([C(15)]-NPY-Dauno-HYD, [C(15)]-NPY-Dauno-MBS, and [C(15)]-NPY-Doxo-MBS) was determined at the human neuroblastoma cell line SK-N-MC, which selectively expresses the NPY Y(1) receptor subtype, and cytotoxic activity was evaluated using a XTT-based colorimetric cellular cytotoxicity assay. The different conjugates were able to bind to the receptor with affinities ranging from 25 to 51 nM, but only the compound containing the acid-sensitive bond ([C(15)]-NPY-Dauno-HYD) showed cytotoxic activity comparable to the free daunorubicin. This cytotoxicity is Y(1) receptor-mediated as shown in blocking studies with BIBP 3226, because tumor cells that do not express NPY receptors were sensitive to free daunorubicin, but not to the peptide-drug conjugate. The intracellular distribution was investigated by confocal laser scanning microscopy. We found evidence that the active conjugate [C(15)]-NPY-Dauno-HYD releases daunorubicin, which is localized close to the nucleus, whereas the inactive conjugate [C(15)]-NPY-Dauno-MBS is distributed distantly from the nucleus and does not seem to release the drug within the cell.
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PMID:Novel peptide conjugates for tumor-specific chemotherapy. 1131 Oct 56

Neuroblastoma, common in children, rarely develops in adults. We recently treated a patient with adult neuroblastoma. A 34-year-old man complained of a swelling in right inguinal region. CT scan showed swelling of retroperitoneal and inguinal lymph nodes, and bone scintigram by 99mTc-HMDP showed an abnormal uptake in the swollen lymph nodes. Chemotherapy with CDDP (cisplatinum), VP-16 (etoposide), BLM (bleomycin), ADM (adriamycin) was not effective. Histopathological examination of a biopsy specimen revealed neuroblastoma. Another chemotherapy with CPM (cyclophosphamide), VCR (vincristine), ADM, DTIC (dacarbazine), CDDP, VP-16 was effective in decreasing the tumor size. Further high dose chemotherapy with CPM, ADM, CDDP, VP-16 combined with peripheral blood stem cell transplantation led to almost complete disappearance of the tumor and normalization of blood tumor markers (neuron specific enolase and immunosuppressive acidic protein). Retroperitoneal lymph node dissection demonstrated well-differentiated neuroblastoma in the excised tissue. Six months postoperatively, the tumor recurred in the pelvic cavity. Although chemotherapy and radiotherapy were given, he died of the disease 12 months postoperatively.
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PMID:[A case of adult neuroblastoma arising in the retroperitoneal space]. 1159 7

Adrenomedullin is a potent vasodilator peptide originally isolated from a pheochromocytoma. Recently, a novel adrenomedullin receptor has been identified as a complex consisting of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 2. To explore possible pathophysiological roles of adrenomedullin and its receptor component RAMP2 in hypoxic tissues, we studied effects of hypoxia on expression of adrenomedullin and RAMP2 in two human neuroblastoma cell lines, IMR-32 and NB69, by radioimmunoassay and Northern blot analysis. Expression levels of adrenomedullin were increased by hypoxia in both cell lines. Treatment with cobalt chloride or desferrioxamine mesylate also increased expression levels of adrenomedullin mRNA. On the other hand, expression levels of RAMP2 mRNA were decreased in IMR-32 cells and were not changed in NB69 cells by hypoxia. Treatment with cobalt chloride or desferrioxamine mesylate decreased expression levels of RAMP2 mRNA in both IMR-32 and NB69 cells. These findings indicate that adrenomedullin expression is induced during hypoxia in IMR-32 and NB69 neuroblastoma cells, but RAMP2 expression is rather suppressed under the same conditions. The decreased expression of RAMP2 and the ADM expression induction under hypoxia may constitute one mechanism of cellular adaptation to hypoxic stress.
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PMID:Differential expression of adrenomedullin and its receptor component, receptor activity modifying protein (RAMP) 2 during hypoxia in cultured human neuroblastoma cells. 1175 65


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