Single-institution experience with matrix coils in the treatment of intracranial aneurysms: comparison with same-center outcomes with the use of platinum coils.

BACKGROUND AND PURPOSE: This study was undertaken to analyze the outcomes and treatment-related complications of the polyglycolic/polylactic acid (PGLA)-coated Matrix platinum coils in the treatment of intracranial aneurysms and compare these results with those derived from the same single-institutional experience with use of uncoated, bare platinum coils. MATERIALS AND METHODS: In this study, we compared 2 groups of patients in a retrospective fashion. The first group consisted of 70 consecutive patients who underwent 82 aneurysm treatments with Matrix coils during the 14-month period of study, from January 2003 to February 2004. We compared this cohort with 70 consecutive patients who underwent a total of 80 aneurysm treatments with bare platinum coils in the 12 months immediately preceding the use of PGLA-coated coils, from January through December 2002. We then recorded the treatment characteristics, angiographic outcomes, and any complications. RESULTS: There were similar baseline demographic characteristics between the 2 study groups except in age, anatomic location, and length of follow-up. The overall recurrence rate of aneurysms was 41% among the Matrix-treated group and 32% among the patients treated with bare platinum. Among the 42 patients treated with 100% Matrix, the rate of recurrence was 31%. Of the recurrences, 21% of the Matrix group, 19% of the 100% Matrix group, and 9% of the bare platinum group required retreatment. The overall rate of complications was 10% in the Matrix-treated group and 7% in the bare platinum group. There was not a statistically significant difference in the rate of recurrence of aneurysms or complications between the 2 groups. CONCLUSIONS: On the basis of our single-center experience, there is insufficient evidence to support the use of Matrix coils over bare platinum coils, given their disadvantages.

Large cell/anaplastic medulloblastomas and medullomyoblastomas: clinicopathological and genetic features.

OBJECT: Medulloblastoma is the most common malignant central nervous system neoplasm found in children. A distinct variant designated large cell/anaplastic (LC/A) medulloblastoma is characterized by frequent dissemination of cerebrospinal fluid (CSF) at presentation and a more aggressive clinical course. The authors report on their examination of the clinicopathological and genetic features of seven such cases encountered at their institution. METHODS: Eighty cases of medulloblastomas were reviewed and seven (8.8%) of these were believed to fit the histological and immunohistochemical criteria for LC/A medulloblastoma. In three cases (43%) either desmoplastic or classic medulloblastoma was the underlying subtype, and in two cases (28%) the LC/A tumor was found within the setting of medullomyoblastoma. Fluorescence in situ hybridization was used in six of the seven cases to characterize the presence of isochromosome 17q, deletion of chromosome 22q (a deletion characteristically found in atypical teratoid/rhabdoid tumors), and c-myc amplification. The patients' clinical histories revealed CSF dissemination in all cases and lymph node metastasis in one case. Isochromosome 17q was found in five (83%) of six cases. Evidence of chromosomal gains indicated aneuploidy in three tumors (50%), and amplification of c-myc was found in three tumors (50%). No 22q deletions were encountered. CONCLUSIONS: A high percentage of LC/A medulloblastomas arise within a background of typical medulloblastomas or medullomyoblastomas. As is the case in conventional medulloblastomas, the presence of 17q is a common early tumorigenic event; however, in a significant percentage of specimens there is also evidence of aneuploidy and/or amplification of c-myc. These findings indicate that LC/A morphological characteristics reflect a more advanced tumor stage than that found in pure medulloblastomas or in typical medullomyoblastomas.

Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia.

Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.

Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline.

The possibility that appropriately designed chemotherapy could act selectively against p53-defective tumor cells was explored in MCF-7 human breast cancer cells. These cells were chosen because they have normal p53 function but are representative of a tumor cell type that does not readily undergo p53-dependent apoptosis. Two sublines (MCF-7/E6 and MCF-7/mu-p53) were established in which p53 function was disrupted by transfection with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. p53 function in MCF-7/E6 and MCF-7/mu-p53 cells was defective relative to control cells in that there were no increases in p53 or p21Waf1/Cip1 protein levels and no G1 arrest following exposure to ionizing radiation. Survival assays showed that p53 disruption sensitized MCF-7 cells to cisplatin (CDDP) but not to several other DNA-damaging agents. CDDP sensitization was not limited to MCF-7 cells since p53 disruption in human colon carcinoma RKO cells also enhanced sensitivity to CDDP. Contrary to the other DNA-damaging agents tested, CDDP-induced DNA lesions are repaired extensively by nucleotide excision, and in agreement with a defect in this process, MCF-7/E6 and MCF-7/mu-p53 cells exhibited a reduced ability to repair a CDDP-damaged chloramphenicol acetyltransferase-reporter plasmid transfected into the cells. Therefore, we attributed the increased CDDP sensitivity of MCF-7 cells with disrupted p53 to defects in G1 checkpoint control, nucleotide excision repair, or both. The G2 checkpoint inhibitor pentoxifylline exhibited synergism with CDDP in killing MCF-7/E6 cells but did not affect sensitivity of the control cells. Moreover, pentoxifylline inhibited G2 checkpoint function to a greater extent in MCF-7/E6 than in the parental cells. These results suggested that, in the absence of p53 function, cancer cells are more vulnerable to G2 checkpoint abrogators. Our results show that a combination of CDDP and pentoxifylline is capable of synergistic and preferential killing of p53-defective tumor cells that do not readily undergo apoptosis.