Citations

Object Spontaneous intracerebral hemorrhage is an uncommon but recognized initial presenting sign of both primary and metastatic brain tumors. The rate of tumor-related intracranial hemorrhage is variably reported from < 1 to 14.6%. Hemorrhage in primary gliomas occurs in 3.7–7.2% of gliomas, mainly in glioblastoma muliforme and oligodendroglioma with low-grade astrocytomas accounting for < 1%. Hemorrhage associated with pilocytic astrocytomas (PAs) is only sporadically reported. The authors report on a series of patients in whom PAs presenting as hemorrhages prompted them to examine the incidence of bleeding in these tumors. Methods Cases involving a confirmed tissue diagnosis of PA from 1994–2005 were reviewed retrospectively. The authors included only patients with evidence of hemorrhage on computed tomography and/or magnetic resonance imaging seen prior to biopsy or resection and in the absence of trauma or other vascular pathological entities. Results In 138 patients with histologically proven PAs, the mean age at diagnosis was 23 years. In 11 patients (8%; 5 male and 6 female) there was evidence of hemorrhage at presentation. There were no locations more susceptible to hemorrhage than any other, although no bleeding occurred within the cerebellum. All but 1 patient was treated with a gross-total resection. Conclusions Hemorrhage in association with PAs likely results from the frequently observed abnormal vasculature in these tumors, occurs with a greater frequency than previously thought, and should be considered in the differential diagnosis of spontaneous intracerebral hemorrhage.

ABSTRACTWe evaluated the participatory role of human HLA-DR molecules in control of virus from the central nervous system and in the development of subsequent spinal cord demyelination. The experiments utilized intracranial infection with Theiler's murine encephalomyelitis virus (TMEV), a picornavirus that, in some strains of mice, results in primary demyelination. We studied DR2 and DR3 transgenic mice that were bred onto a combined class I-deficient mouse (beta-2 microglobulin deficient; β2m0) and class II-deficient mouse (Aβ0) of theH-2bbackground. Aβ0.β2m0mice infected with TMEV died within 18 days of infection. These mice showed severe encephalomyelitis due to rapid replication of virus genome. In contrast, transgenic mice with insertion of a single human class II major histocompatibility complex (MHC) gene (DR2 or DR3) survived the acute infection. DR2 and DR3 mice controlled virus infection by 45 days and did not develop spinal cord demyelination. Levels of virus RNA were reduced in HLA-DR transgenic mice compared to Aβ0.β2m0mice. Virus-neutralizing antibody responses did not explain why DR mice survived the infection and controlled virus replication. However, DR mice showed an increase in gamma interferon and interleukin-2 transcripts in the brain, which were associated with protection. The findings support the hypothesis that the expression of a single human class II MHC molecule can, by itself, influence the control of an intracerebral pathogen in a host without a competent class I MHC immune response. The mechanism of protection appears to be the result of cytokines released by CD4+T cells.

Abstract Purpose: MicroRNA (miRNA) is a new class of small, noncoding RNA. The purpose of this study was to determine if miRNAs are differentially expressed in hepatocellular carcinoma (HCC). Experimental Design: More than 200 precursor and mature miRNAs were profiled by real-time PCR in 43 and 28 pairs of HCC and adjacent benign liver, respectively, and in normal liver specimens. Results: Several miRNAs including miR-199a, miR-21, and miR-301 were differentially expressed in the tumor compared with adjacent benign liver. A large number of mature and precursor miRNAs were up-regulated in the adjacent benign liver specimens that were both cirrhotic and hepatitis-positive compared with the uninfected, noncirrhotic specimens (P &lt; 0.01). Interestingly, all of the miRNAs in this comparison had increased expression and none were decreased. The expression of 95 randomly selected mRNAs was not significantly altered in the cirrhotic and hepatitis-positive specimens, suggesting a preferential increase in the transcription of miRNA. Comparing the miRNA expression in the HCC tumors with patient's survival time revealed two groups of patients; those with predominantly lower miRNA expression and poor survival and those with predominantly higher miRNA expression and good survival (P &lt; 0.05). A set of 19 miRNAs significantly correlated with disease outcome. A number of biological processes including cell division, mitosis, and G1-S transition were predicted to be targets of the 19 miRNAs in this group. Conclusion: We show that a global increase in the transcription of miRNA genes occurs in cirrhotic and hepatitis-positive livers and that miRNA expression may prognosticate disease outcome in HCC.

Object Bioluminescence imaging (BLI) offers a rapid and accurate means for longitudinal study of tumor cell growth and response to therapy in rodent models. Because this technology has only recently come into use in the field of small animal imaging, applications in this area have been limited. In the current study we have applied BLI to the analysis of clinically relevant issues involving use of the DNA methylating agent temozolomide (TMZ) in a mouse model. Methods An invasive glioblastoma multiforme xenograft was modified for BLI via transduction with a luciferase-encoding lentivirus. Supratentorial tumors were established in athymic nude mice that were subsequently assigned randomly to control and TMZ treatment groups, and the extent of intracranial tumor was monitored using BLI. Results In an experiment designed to compare the extent of antitumor effect between a single high-dose TMZ treatment and a protracted low-dose TMZ regimen, BLI revealed the protracted regimen as having superior antitumor effect, and this interpretation was consistent with results from a survival comparison between the two TMZ treatment groups. In a second experiment designed to assess the utility of BLI for testing therapies against recurrent glioblastoma multiforme, mice with intracranial tumors were retreated with TMZ at a time when BLI monitoring revealed tumor regrowth following initial TMZ treatment, and retreatment was successful in providing additional survival benefit. Conclusion The results of these experiments indicate that BLI monitoring can be used as a surrogate for predicting survival benefit from TMZ treatment, permits early determination of relative survival benefit associated with distinct TMZ therapeutic regimens, and offers a means of investigating secondary/salvage therapy efficacy following tumor regrowth from initial therapy.

✓ The authors report on a patient without neurofibromatosis Type 1 or 2 (NF1 or NF2) and without evidence of schwannomatosis, who was found to have an unusual combination of nerve sheath tumors—a large cellular schwannoma and multifascicular involvement of a plexiform neurofibroma arising from the same site within the radial nerve and posterior cord of the infraclavicular brachial plexus. This case broadens the spectrum of combined pathological features of nerve sheath tumors. Genetic studies revealed a combined loss of neurofibromin and merlin in both regions and chromosome arm 22q deletion within the neurofibroma component only. The latter finding supports the suggestion that these were two different clonal neoplasms, and is consistent with a collision tumor pattern.

AbstractBackgroundPatients with papillary thyroid carcinoma (PTC) may suffer recurrence despite thyroidectomy and complete radioiodine (RAI) ablation. Reoperation is vitally dependent on accurate and complete disease localization, typically utilizing cervical ultrasonography (US) and/or computed tomography. Our aim was to determine the comparative value of F18‐fluorodeoxyglucose positron emission tomography (PET) to US for localization of locoregional recurrence in patients who underwent reoperation for recurrent PTC.MethodsFrom 1999 to 2004, 30 patients who underwent re‐exploration and 100 nonoperated patients who were investigated with PET for possible recurrent PTC were reviewed. The surgical group [9 males, 21 females; mean age = 50 years (range = 18–84 years)] all had received RAI ablation. Preoperative thyroid‐stimulating hormone (TSH), thyroglobulin (Tg), and location of metastasis were recorded for each imaging study and surgical exploration. All separate sites that contained disease pathologically must have been identified by imaging for a patient to be considered true positive (TP).ResultsPET scans were TP in 43%, false positive in 7%, false negative (FN) in 50%, and had a sensitivity of 46%. Comparable US results were 86%, 10%, 3%, and 96%. Of the 15 patients with FN PET scans, 13 had lymph node metastasis less than 2 cm in diameter, 11 had Tg ≤ 10 μg/L, and the TSH < 20 in 13. In only 3 of the 30 (10%) patients was PET deemed to add value.ConclusionsAt least with suppressed TSH, PET scanning in reoperative PTC patients appears to offer modest benefit beyond high‐resolution US.