Posterior fossa recurrence of WHO grade II and III supratentorial gliomas.

OBJECTIVE/BACKGROUND: Posterior fossa (PF) recurrences of supratentorial (ST) World Health Organization (WHO) grade II and III gliomas are thought to be rare and to have grim prognoses. METHODS: This study entailed searching through our database and reviewing the records of patients with grade II and III ST gliomas who developed PF recurrence with no overt secondary gliomatosis or leptomeningeal spread. RESULTS: Of 2266 grade II and III gliomas, 14 fulfilled the inclusion criteria: 5 oligodendrogliomas (O; 1 OII, 4 OIII); 7 astrocytomas (A; 4 AII, 3 AIII); and 2 oligoastrocytomas (OA; both OAIII). The male/female gender ratio was 10/4, and median age at recurrence was 43 years. Two groups were identified. In one group (n=8; 1 AII, 3 AIII, 2 OAIII, 2 OIII), a rapidly growing contrast-enhancing PF mass (6/8) was associated with ST progression, and median survival time after detection was only 6.5 months despite radiotherapy and/or chemotherapy. In the second group (n=6; 3 AII, 1 OII, and 2 OIII), a non-contrast-enhancing (5/6), asymptomatic (5/6), slow-growing PF mass remained isolated, and treatment with radio- or chemotherapy produced objective responses in three patients and durable stabilization in the remaining three. After a median follow-up of 63months, only one patient died due to delayed recurrence of the ST lesion, while the remaining five patients are still alive. CONCLUSION: Non-contiguous PF relapses of ST grade II and III gliomas are rare. A high-grade ST tumor that is concomitantly progressing appears to be a predictor of poor survival. Conversely, the tumor course may be indolent if the ST lesion is low-grade and non-progressive at the time of PF involvement. The possible mechanism(s) behind this tropism are also discussed.

Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation.

For differentiation-defective malignancies, compounds that modulate transcription, such as retinoic acid and histone deacetylase (HDAC) inhibitors, are of particular interest. HDAC inhibitors are currently under investigation for the treatment of a broad spectrum of cancer diseases. However, one clinical drawback is class-specific toxicity of unselective inhibitors, limiting their full anticancer potential. Selective targeting of individual HDAC isozymes in defined tumor entities may therefore be an attractive alternative treatment approach. We have previously identified HDAC family member 8 (HDAC8) as a novel target in childhood neuroblastoma. Using small-molecule inhibitors, we now demonstrate that selective inhibition of HDAC8 exhibits antineuroblastoma activity without toxicity in two xenograft mouse models of MYCN oncogene-amplified neuroblastoma. In contrast, the unselective HDAC inhibitor vorinostat was more toxic in the same models. HDAC8-selective inhibition induced cell cycle arrest and differentiation in vitro and in vivo. Upon combination with retinoic acid, differentiation was significantly enhanced, as demonstrated by elongated neurofilament-positive neurites and upregulation of NTRK1. Additionally, MYCN oncogene expression was downregulated in vitro and tumor cell growth was markedly reduced in vivo. Mechanistic studies suggest that cAMP-response element-binding protein (CREB) links HDAC8- and retinoic acid-mediated gene transcription. In conclusion, HDAC-selective targeting can be effective in tumors exhibiting HDAC isozyme-dependent tumor growth in vivo and can be combined with differentiation-inducing agents.

Versatility in computer automation for biofeedback: the behavioral assessment and rehabilitative training system (BARTS).

User versatility in a system for computer-automated biofeedback training is the degree to which the assessment and training parameters may be altered by the user's employing English language or other simple code, that is, without altering the system's applications software. The Behavioral Assessment and Rehabilitative Training System (BARTS) includes a design and control program that allows for the specification of assessment and training protocols by persons who are entirely lacking in computer programming skills. This paper describes the logic for data acquisition and training that is incorporated in the BARTS, describes the parameters that must be specified in constituting unique assessment or training protocols, and illustrates the system's application in a research-oriented biofeedback clinic.

Morphology and ultrastructure of a Penicillium sp. grown on n-hexadecane or peptone.

The morphology and ultrastructure of a Penicillium sp. grown on n-hexadecane or on peptone in shake-culture were compared using transmission and scanning electron microscopy. The fungus grew as hollow mycelial balls surrounding individual hydrocarbon droplets on n-hexadecane and as solid mycelial balls on peptone. A dense layer of fungal mycelium that showed irregular forms, fusion, and increase in hyphal size formed at the hydrocarbon-water interface. Inclusions were present in the hexadecane-grown fungus that were absent when the Penicillium sp. was grown on peptone. Problems of fixation made it difficult to differentiate detailed changes in the cytoplasm when the fungus was examined with the transmission electron microscope.