ABSTRACT
A 13-year-old girl presented with an exceedingly rare case of primary yolk sac tumor located within the lateral ventricle, manifesting as headache, nausea, and diplopia. Magnetic resonance imaging revealed a 4-cm-diameter solid enhanced mass within the left inferior horn of the lateral ventricle. The tumor was removed subtotally via left middle temporal corticotomy. The histological and immunohistochemical diagnosis was pure yolk sac tumor. The serum alpha-fetoprotein (AFP) level was elevated at 1957.2 ng/ml and the serum beta-human chorionic gonadotropin level was 4 mIU/ml after surgery. The patient underwent radiotherapy (whole brain, 30 Gy; tumor bed, 21 Gy; whole spinal axis, 30 Gy) and chemotherapy (ifosfamide, cisplatin, etoposide). After three treatment cycles, the serum AFP level had decreased to 4.5 ng/ml. However, the tumor recurred with cerebrospinal fluid dissemination after nine cycles of chemotherapy. She died 18 months after surgery. The possibility of germ cell tumor should be considered in pediatric patients with brain tumors occurring outside the pineal or suprasellar region.
Subject(s)
Brain/pathology , Cerebral Ventricle Neoplasms/diagnosis , Endodermal Sinus Tumor/diagnosis , Lateral Ventricles/pathology , Adolescent , Biomarkers, Tumor/analysis , Biomarkers, Tumor/blood , Brain/anatomy & histology , Brain/surgery , Cerebral Ventricle Neoplasms/therapy , Chorionic Gonadotropin, beta Subunit, Human/blood , Diplopia/etiology , Drug Therapy , Endodermal Sinus Tumor/therapy , Fatal Outcome , Female , Headache/etiology , Humans , Hydrocephalus/etiology , Intracranial Hypertension/etiology , Lateral Ventricles/surgery , Magnetic Resonance Imaging , Nausea/etiology , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neurosurgical Procedures , Radiotherapy , Ventriculostomy , alpha-Fetoproteins/metabolismABSTRACT
BACKGROUND: Low-intensity ultrasound showed tumor cell killing by a non-thermal effect in human leukemia cells. The aim of our study was to investigate the efficacy of low-intensity ultrasound on malignant astrocytic tumor cells with the photosensitizer, Photofrin, which is taken up by the cell surface receptor, low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP/alpha2MR). MATERIALS AND METHODS: Cells were sonicated with continuous wave ultrasound with or without the presence of Photofrin (75 mg/ml) at an intensity of 0.3 W/cm(2) for a duration of 5, 15, or 30 s. RESULTS: Ultrasound alone induced instant cell killing immediately after sonication in both U251MG and U105MG malignant gliomas cells. In U251MG cells, which expressed LRP/alpha2MR, significant enhancement of cell killing was observed following Photofrin pretreatment, 52.7+/-17.5%, 13.0+/-4.6% and 3.9+/-0.9% for 5, 15, and 30 s respectively (p<0.05). This enhancement of cell killing was abolished by preincubation with receptor-associated protein (RAP) which binds specifically to LRP/alpha2MR. This enhancement by Photofrin was not achieved in U105MG which did not express LRP/alpha2MR. U251MG cells accumulated 2.43+/-0.25 Photofrin mg/mg protein, which significantly decreased with RAP pretreatment (1.38+/-0.22 Photofrin mg/mg protein) (p<0.05). U105MG cells accumulated 1.31+/-0.16 Photofrin mg/mg protein, which was significantly less than in U251MG cells. Photofrin uptake was not altered by RAP pretreatment in U105MG cells. U251MG cells exposed to ultrasound in the presence of Photofrin showed multiple surface pores and dimple-like craters. CONCLUSION: This is the first report to demonstrate the usefulness of low-intensity ultrasound for the cell killing of malignant glioma cells. Antitumor activity might be enhanced by combination with photosensitizer, which is transported by cell surface LRP/alpha2-MR to some degree.
Subject(s)
Brain Neoplasms/therapy , Cell Survival/drug effects , Dihematoporphyrin Ether/therapeutic use , Glioma/therapy , Photosensitizing Agents/therapeutic use , Ultrasonic Therapy , Brain Neoplasms/pathology , Combined Modality Therapy , Glioma/pathology , Humans , Low Density Lipoprotein Receptor-Related Protein-1/genetics , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , alpha-Macroglobulins/genetics , alpha-Macroglobulins/metabolismABSTRACT
BACKGROUND: This study assessed safety and efficacy for intratumoral administration of tumor necrosis factor-a (TNF-SAM2) into the post-operative tumor cavity through an Ommaya reservoir for patients with malignant glioma. MATERIALS AND METHODS: Seven patients with malignant glioma, comprising 3 cases with glioblastoma multiforme (GBM), 3 cases with anaplastic astrocytoma (AA) and 1 case with malignant ependymoma (ME) were included in the study. All patients were pathologically diagnosed and initially treated with adjuvant therapy (radiation and/or ranimustine and/or systemic TNF-SAM2 infusion) following surgical resection. TNF-SAM2 was administrated into the post-operative tumor cavity through a reservoir at a concentration of 1x10(4) U/body when recurrence was detected, or as initial induction therapy concomitant with radiotherapy. RESULTS: Partial response to this regional immunotherapy was seen in 4 out of 7 patients, and 1 patient with GBM has remained clinically stable for >184 weeks without tumor progression. With AA, 2 cases appeared to display slowed advance and longer times to tumor recurrence or regrowth. No serious adverse effects, such as brain edema, hemorrhage or seizure were observed, nor systemic toxicities. CONCLUSION: Local immunotherapy with TNF-SAM2 may safely contribute to therapeutic efficacy in some patients with malignant glioma.
Subject(s)
Glioma/therapy , Tumor Necrosis Factor-alpha/administration & dosage , Adult , Aged , Female , Glioma/immunology , Humans , Injections, Intralesional , Male , Middle Aged , Treatment Outcome , Tumor Necrosis Factor-alpha/adverse effectsABSTRACT
OBJECT: The authors investigated the presence of endoglycosidase heparanase in human glioblastoma multiforme (GBM) and metastatic brain tumors as well as in healthy brain tissue to explore the relationship between the biological characteristics of GBM and the role of heparanase. METHODS: Heparanase messenger (m)RNA was almost undetectable in GBMs in vivo, whereas it was frequently seen in metastatic brain tumors according to results of reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical analysis of paraffin-embedded tissue sections showed that neoplastic cells in metastatic brain tumors, especially in cells that invaded blood vessels, exhibit intense heparanase immunoreactivity. Heparanase was present in two highly invasive glioma cell lines, U87MG and U251MG, in vitro. These cell lines did not have metastatic capability, which was tested in an experimental pulmonary metastases model in mice. The activity of heparanase in these cell lines was almost the same as that in the highly metastatic melanoma cell line B16-F1. After nude mice were inoculated with U87MG cells, however, heparanase was no longer detected in subcutaneous or intracerebral experimental glioma in vivo based on results of immunohistochemical analysis. According to results of real-time quantitative PCR, there was a 10-fold increase in heparanase mRNA in U87MG glioma cells in vitro compared with that in experimental U87MG glioma tissue in vivo in nude mice. CONCLUSIONS: These results indicate that the expression of heparanase was downregulated in GBM in vivo, which rarely metastasizes to distant organs outside the central nervous system. Heparanase is not implicated in the invasiveness of GBM to surrounding healthy brain tissue in vivo.
Subject(s)
Brain Neoplasms/enzymology , Glioblastoma/enzymology , Glucuronidase/analysis , Animals , Down-Regulation , Female , Glucuronidase/genetics , Humans , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Local invasive infiltration and growth are key features in glioblastoma, which are accompanied by remodeling of the vasculature and the destruction of the surrounding normal brain tissues. The local and regional spread of glioblastoma is often associated with poor prognosis. The invasive character of glioblastoma appears to depend partly on the proteolytic destruction of the extracellular matrix components. In this article, we review the role of proteolytic enzymes, urokinase-type plasminogen activator and matrix-metalloproteases, for diffuse infiltrative growth of glioblastoma. An understanding of the mechanisms of increased expression of these molecules in glioblastoma might provide an insight into the regulatory pathway of cellular invasion and for a new therapeutic strategy for glioblastoma.