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PubMed1990

Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial.

Between October 1985 and March 1988, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase II trial of carboplatin 560 mg/m2 every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 21 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/microliters, and 37% had platelet count nadirs less than 25,000/microliters. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity.

Adolescent↗
PubMed1983

Childhood cancer incidence: geographical and temporal variations.

Data from the first four volumes of Cancer Incidence in Five Continents (CI-5) and from the first 5 years of the US Surveillance, Epidemiology and End Results (SEER) program were analyzed for evidence of geographical and temporal variations in the incidence of selected childhood tumors. Only lymphoid leukemia and glial neoplasms are common enough for the observed differences between US registries to be distinguished from sampling variation. Internationally, kidney and eye tumors and leukemia show less geographical variation than do lymphomas and brain tumors, but for none of the tumors examined is the incidence constant. Wilms' tumor rates among Japanese, Singapore Chinese and Indians (Bombay) are approximately 60% of the rates in North America and Britain, whereas in Scandinavia the rates are up to 30% higher. This lessens the status of Wilms' tumor as an "index tumor" of childhood. Areas or countries with especially high or low rates of other tumors are identified. Rates for glial neoplasms (SEER data) and Hodgkin's disease (CI-5) are increasing with time in the US, while brain tumors are being diagnosed more frequently worldwide. However, the results for brain tumors may largely reflect changes in pathology diagnosis or reporting practices, and those for Hodgkin's disease may reflect improvements in case ascertainment. Otherwise, there is a remarkable stability in the incidence of selected childhood cancers over time.

Adolescent↗
PubMed1995

Carboplatin in childhood medulloblastoma/PNET: feasibility of an in vivo sensitivity test in an "up-front" study.

Sixteen patients with high risk MB/PNET at diagnosis were included in a pilot study employing carboplatin (CBDCA) as a single drug prior to conventional therapy. The main goal of the study was to identify in a short-term trial a significant response that would predict further response to CBDCA in the single patient. Exploration of CBDCA activity was focused on response after the first course as compared to the response following the second course. A course consisted of CBDCA 600 mg/m2 on days 1 and 2 administered in a 1 h infusion to be repeated 3-4 weeks later. After two cycles we observed 1 CR and 9 PR, that is a 62% response rate. The first course resulted in 5 PR, 5 MR, 5 SD, and 1 PD; after the subsequent course in all responding patients, response persisted or improved whereas in no patient with SD any improvement was observed. The correlation of response to the first course with response to the second course was statistically significant (P = 0.0009). The main toxicity of the single course was hematologic and consisted of rapidly reversible grade 3-4 neutropenia and thrombocytopenia in 94% of patients. Pharmacokinetic studies showed a very limited interpatient variability of both Cmax 57.6 +/- 9.9 micrograms/ml) and AUC (15.3 +/- 1.5 mg/ml.min) of free CBDCA, which eliminates an important variable in the evaluation of response. In conclusion, this "in vivo test" appears effective, reasonably safe, and reproducible in identifying patients likely to benefit from CBCDA: after a period of time as short as 3-4 weeks following the first course, multidrug chemotherapy including CBDCA may be employed in the responding patients, whereas an alternative regimen would be indicated in the non-responding patients.

Adolescent↗
PubMed1996

Study of the antioxidant enzymes in human brain tumors.

The activities of antioxidant enzymes i.e. Cu, Zn-SOD, Mn-SOD, CAT, and GSH-Px in the normal brain and brain tumors, as well as the two varieties of SOD in the mitochondria were examined and correlated to the histopathological diagnosis and the degree of malignancy of tumors. It was found that these scavenging enzymes of oxygen free radicals were expressed with great regularity in brain tumors. Both Cu, Zn-SOD and Mn-SOD were decreased in descending order in meningiomas, low grade astrocytomas, high grade astrocytomas and medulloblastomas. Furthermore, the reduction of Mn-SOD in mitochondria was proportionate to that of the whole tissues. While in contrast to the SODs, the CAT levels were significantly increased in ascending order in high grade astrocytomas, low grade astrocytomas and meningiomas. GSH-Px increased in meningiomas but not in gliomas.

Antioxidants↗
PubMed1990

Prediction of the interaction effects Ar+ laser-brain tumours by study of the photoacoustic spectroscopy of cerebral oncotypes.

A preliminary definition of light absorption spectra of brain neoplasm represents a correct approach to the laser therapy of cerebral tumours. The goal should be the identification of those oncotypes more sensive to the laser energy, allowing consequently a dosage of the energy proportional to the light absorption coefficient, reducing any side effects. With this purpose the coefficients of light-absorption of 63 different brain tumours have been analyzed and defined by means of photocoustic spectrometry. The study has been focused at wavelength of the Ar+ laser (4,600-6,000 A). The results show a close relationship between histology, degree of vascularization and/or pigmentation and light absorption: the more immature and/or pigmented oncotypes show the highest coefficients of optical absorption. In the laser therapy of these neoplasms it will be sufficient to use low powers and short exposure time.

Animals↗
PubMed2004

Synergistic cytotoxicity of the ribonucleotide reductase inhibitor didox (3,4-dihydroxy-benzohydroxamic acid) and the alkylating agent carmustine (BCNU) in 9L rat gliosarcoma cells and DAOY human medulloblastoma cells.

PURPOSE: Ribonucleotide reductase (RR) is the rate-limiting enzyme of de novo DNA synthesis and has been shown to be upregulated linked with proliferation and malignant transformation. It was therefore identified as an excellent target for antitumor therapy. In the present study we investigated the biochemical and cytotoxic effects of didox, an inhibitor of RR, as a single agent and in combination with BCNU, an alkylating anticancer drug, in 9L rat gliosarcoma cells and DAOY human medulloblastoma cells. METHODS: The effect of didox on the intracellular concentrations of deoxynucleosidetriphosphates (dNTPs) was studied in 9L cells. Pool sizes were determined by HPLC. In addition, the cytotoxic effects of didox and BCNU as single drugs and in equimolar combination were tested in 9L and in DAOY cells. Combination effects were determined according to the equation of Chou and Talalay. The expression of DNA repair-related genes was determined after exposure of 9L cells to BCNU, didox and a combination of the two compounds, using a cDNA array. RESULTS: Incubation of 9L cells with 30 microM didox for 24 h significantly decreased the intracellular concentrations of the DNA precursors dCTP (61% of control) and dGTP (17% of control), and significantly increased the concentration of dATP (155% of control). This dNTP imbalance compromised DNA synthesis and repair and might therefore have been, at least in part, responsible for the highly synergistic cytotoxic effects seen when BCNU was used simultaneously with didox in 9L and in DAOY cells. With almost all combinations tested, highly synergistic effects were seen, as indicated by combination indices of <1 according to the equation of Chou and Talalay. In 9L cells, BCNU upregulated the expression of DNA repair-associated genes, whereas coincubation of the cells with didox reduced overexpression of some of these repair-related genes. CONCLUSION: A combination of BCNU and didox was proven to act in a synergistic manner in two cell lines, 9L rat gliosarcoma and DAOY human medulloblastoma cells. Further in vivo tests using these two compounds systemically and/or locally at the tumor site might be warranted.

Animals↗
PubMed1974

Jaw metastases.

Explore the source record for details and available documents.

Adenocarcinoma, Mucinous↗
PubMed1986

Computed tomography findings of severe mineralizing microangiopathy in the brain.

The intracranial CT findings of mineralizing microangiopathy, a rare condition, are described in seven patients. The underlying pathology was posterior fossa medulloblastoma (four patients), cerebelloastrocytoma (two patients), and acute lymphatic leukemia (one patient). Each of the seven patients was less than 10 years old. Dystrophic calcification was present in the corticomedullary junction, lentiform nucleus of the basal ganglia, corticomedullary junction, and dentate nucleus of the cerebellum. Three of the patients had subtle neurologic signs related to the mineralizing microangiopathy, but none died of central nervous system disease. Although three factors--radiation therapy, chemotherapy, and increased intracranial pressure--probably have a synergistic role in the pathogenesis, radiation is believed the dominant factor. The minimum dose required to induce this damage is 2000 rad.

Astrocytoma↗
PubMed1999

Longstanding trigeminal sensory neuropathy of nontraumatic cause.

OBJECTIVE: Trigeminal sensory neuropathy is an uncommon but often significant orofacial symptom. There are few detailed descriptions of the problem in the dental literature. The aim of this study was to evaluate the clinical presentation and management of a cohort of patients presenting with anesthesia/paresthesia affecting one or more divisions of the trigeminal nerve unrelated to any identifiable traumatic cause. STUDY DESIGN: Nine patients with trigeminal neuropathy were examined. Each patient underwent a standard protocol of examination and hematologic, serologic, radiologic, and histopathologic investigations, as appropriate. RESULTS: Trigeminal neuropathy was found to be secondary to distant malignancy in 4 patients and to connective tissue disease in 2 patients. In each of 3 other patients, there was no obvious cause for the neuropathy. Patients with malignancy as the cause of their neuropathy tended to have involvement of more than one division of the trigeminal nerve and/or other neurologic features. CONCLUSIONS: Trigeminal sensory neuropathy may herald underlying distant malignancy or connective tissue disease. Anesthesia and paresthesia of the orofacial region are therefore serious clinical symptoms that must be carefully investigated before a diagnosis of idiopathic disease is made.

Adenocarcinoma↗
PubMed1974

Metastatic medulloblastoma.

The incidence of metastatic medulloblastoma is probably greater than the thirteen documented patients. Case reports of metastatic medulloblastoma must be carefully analysed. We have added two cases which conform to Weiss' criteria for metastatic disease. The direction and factors influencing spread have been discussed.

Adrenal Gland Neoplasms↗
PubMed1999

Progressive disease in children with medulloblastoma/PNET during preradiation chemotherapy.

The overall prognosis in children with medulloblastoma/PNET has not significantly improved over the past decade. Intensive neoadjuvant chemotherapy has not yet adequately explored. We evaluated the short-term clinical results of an intensive chemotherapy regimen in high risk children with newly diagnosed MB/PNET, after surgery and before radiation. Twelve previously untreated patients with high-risk medulloblastoma/PNET, according to Chang's classification, were treated with the following chemotherapy regimen: high dose carboplatin 600 mg/m2/day on days 1 and 2; the same course was administered 4 weeks later. One month later, high dose cyclophosphamide 2 g/m2/day on days 1 and 2, followed by an identical course 4 weeks later. Vincristine 1, 5 mg/m2 i.v. was given on the first day of each course. Systemic evaluation of the disease included imaging of the entire neuraxis, including MRI of the entire spine. Out of 12 enrolled, 7 patients were able to be evaluated for a residual disease after surgery. After two cycles of high dose carboplatin, we noted 1 CR, 4 PR and 2 MR. After the subsequent two cycles of high dose cyclophosphamide we observed an additional response in 4 cases. On the other hand, 4 patients clearly showed evidence of PD immediately after the first course of cyclophosphamide (2 cases) or following the second course. Three of the 4 patients had shown respectively 1 CR and 2 PR after the second course of carboplatin. Whereas it was confirmed that 2 courses of high dose carboplatin is effective in high risk MB/PNET children, we observed an unacceptable number of PD during the subsequent high dose cyclophosphamide therapy. A review from the literature also suggests that, in general, the longer radiotherapy is delayed, the higher the incidence of PD. In the search for the optimal drug combination in "sandwich chemotherapy" for children with high risk MB/PNET, PD must be reduced to an acceptable incidence, since a high number of PD may significantly lower the probability of long-term survival.

Adolescent↗