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)

High energy beta-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. We developed as carriers for the ionic form of 90Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe3O4 (magnetite) which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 microns MMS were radiochemically loaded to high specific activity with 90Y at a pH of 5.7. Stability studies showed that approximately 95% of added 90Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 degrees C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. We are currently optimizing this system for use in the treatment of neoplastic meningitis.
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PMID:Magnetically directed poly(lactic acid) 90Y-microspheres: novel agents for targeted intracavitary radiotherapy. 798 88

From 1991 to 1995, we reviewed the medical records of 200 pediatric patients with systemic malignancies to study the occurrence of neurologic complications and their treatment. A total of 25 patients with neurologic complications were found. Complications included intracranial metastasis (one patient), intraspinal metastasis (one), spinal epidural compressions (three), leptomeningeal metastases (six), metabolic encephalopathy (10), opportunistic infection (one), cerebrovascular disorders (three), treatment complications (six) and paraneoplastic syndromes (two). Ten patients had seizures. One patient with acute lymphoblastic leukemia (ALL) had the unusual complication of cytomegalovirus retinitis and glaucoma. Seven patients had neurologic features at presentation. ALL was the most common malignancy (56%) and neuroblastoma (20%) was the second. Neurologic deficits are frequently seen in pediatric patients with systemic malignancies and can, in fact, be the presenting signs. Early diagnosis and treatment is important to prevent further neurologic disability.
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PMID:Neurologic complications of pediatric systemic malignancies. 885 52

Labeling of specific antibodies with bifunctional chelated Actinium-225 ((225)Ac; an alpha generator) allows the formation of new, highly potent and selective alpha-emitting anticancer drugs. We synthesized and evaluated a radioimmunoconjugate based on 3F8, an IgG(3) antibody that specifically binds to ganglioside GD2, which is overexpressed by many neuroectodermal tumors including neuroblastoma. The (225)Ac-1,4,7,10-tetra-azacylododecane (DOTA)-3F8 construct was evaluated for radiochemical purity and sterility, immunoreactivity, cytotoxicity in vitro, induction of apoptosis on GD2-positive cells, as well as for pharmacological biodistribution and metabolism of the (225)Ac generator and its daughters in a nude mouse xenograft model of neuroblastoma. The (225)Ac-3F8 showed an IC(50) of 3 Bq/ml (80 pCi/ml) on the neuroblastoma cell line, NMB7, in vitro. Apoptosis of these cells was not observed. Biodistribution in mice showed specific targeting of a subcutaneous tumor; there was redistribution of the (225)Ac daughter nuclides mainly from blood to kidneys and to small intestine. Toxicity was examined in cynomolgus monkeys. Monkeys injected with 1 to 3 doses of intrathecal (225)Ac-3F8 radioimmunoconjugate (80 to 150 kBq/kg total dose) did not show signs of toxicity based on blood chemistry, complete blood counts, or by clinical evaluations. Therapeutic efficacy of intrathecal (225)Ac-3F8 was studied in a nude rat xenograft model of meningeal carcinomatosis. The (225)Ac-3F8 treatment improved survival 2-fold from 16 to 34 days (P = 0.01). In conclusion, in vivo alpha generators targeted by 3F8 warrant additional study as a possible new approach to the treatment of carcinomatous meningitis.
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PMID:Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of alpha-emitting atomic nanogenerators targeting disialo-ganglioside GD2. 1550 78

Intrinsic biologic tumor features are critical prognosticators of survival in patients with neuroblastoma. Patients with localized neuroblastoma and favorable biologic parameters may be observed without treatment. Conversely, leptomeningeal metastases in patients with primary extracranial neuroblastoma are highly unusual and, despite aggressive multimodality therapies, invariably fatal. The authors describe a newly diagnosed infant with neuroblastoma and radiographic imaging suggestive of leptomeningeal metastases. The patient underwent partial surgical resection of the primary tumor. The primary tumor revealed favorable biologic characteristics. The patient was observed with no cytotoxic therapy and remained well with no evidence of disease progression more than 3 years since diagnosis. This case illustrates that some infants with favorable-biology neuroblastoma may be observed without treatment despite the advanced INSS stage.
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PMID:Favorable-biology neuroblastoma presenting with leptomeningeal metastases?: a case presentation. 1554 2

A 3-year-old male, diagnosed with stage 4 neuroblastoma, developed recurrent leptomeningeal metastasis after multi-modality treatment including multi-agent chemotherapy, surgery, high dose chemotherapy plus stem cell rescue, cis-retinoic acid and intravenous (IV) topotecan. He then received intraommaya (IO) topotecan three times weekly (maximum dose; 0.4 mg). A complete response was achieved by a resolution of malignant cells in cerebrospinal fluid and resolution leptomeningeal enhancement by brain MRI. Treatment toxicities included low-grade fever and minimal headache. The duration of treatment response from IO topotecan was 18 weeks. The survival time from CNS recurrence in this patient was 13 months. We suggest IO topotecan be considered for neoplastic meningitis of tumors with known sensitivity to topotecan.
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PMID:Favorable response of intraommaya topotecan for leptomeningeal metastasis of neuroblastoma after intravenous route failure. 1657 4

Neoplastic meningitis is being recognized with increasing frequency in patients with cancer: the common causes being adenocarcinomas originating from the lung, stomach, breast, ovary, malignant melanoma, leukemia, lymphoma, Ewings sarcoma, rhabdomyosarcoma, retinoblastoma and primary CNS malignancies. Meningeal metastases, though rare can be seen in advanced stages of neuroblastoma. Recognition of meningeal metastases is crucial for successful diagnosis and prompt treatment of these patients. Here, we present two patients of neuroblastoma in whom positron emission tomography-computed tomography (PET-CT) examination resulted in detection of meningeal metastases at diagnosis; thus, emphasizing the need of inclusion of brain imaging in PET-CT protocol in all cases of advanced neuroblastoma.
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PMID:PET-CT in detection of meningeal metastasis in neuroblastoma. 1913 63

Disseminated carcinomatosis of the bone marrow (DCBM) is a condition in which bone marrow (BM) metastases diffusely invade the BM, and is frequently accompanied by disseminated intravascular coagulation (DIC). While prostate, lung, breast and stomach malignancies, in addition to neuroblastoma, are the most prevalent non-hematological malignancies to metastasize frequently to the BM, colorectal cancer is a malignancy that rarely metastasizes to the BM. The present case describes a 65-year-old male patient treated by resection and one course adjuvant chemotherapy for stage IIIC rectal cancer who presented with nasal bleeding at 8 months post-surgery. A blood test exhibited DIC. A BM biopsy was performed and the definitive diagnosis was DCBM with DIC. Promptly, anti-DIC treatment and chemotherapy with a modified FOLFOX6 (folinic acid, leucovorin (LV), 5-fluorouracil (5-FU) and oxaplatin) regimen was started. Following 1 cycle of chemotherapy, DIC was improved and subsequent to 2 cycles of modified FOLFOX6 the patient was discharged. The patient was alive 263 days subsequent to the diagnosis of DIC, but succumbed to carcinomatous meningitis as a result of disease progression. To the best of our knowledge, this is the first report of DCBM with DIC of curatively resected rectal cancer as the first presentation of relapse that was successfully treated with aggressive therapy, including chemotherapy.
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PMID:Disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation as the first symptom of recurrent rectal cancer successfully treated with chemotherapy: A case report and review of the literature. 2859 29