ABSTRACT
Transforming growth factor-beta2 (TGF-beta2) is known to suppress the immune response to cancer cells and plays a pivotal role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. For targeted protein suppression the TGF-beta2-specific antisense oligodeoxynucleotide AP 12009 was developed. In vitro experiments have been performed to prove specificity and efficacy of the TGF-beta2 inhibitor AP 12009 employing patient-derived malignant glioma cells as well as peripheral blood mononuclear cells (PBMCs) from patients. Clinically, the antisense compound AP 12009 was assessed in three Phase I/II-studies for the treatment of patients with recurrent or refractory malignant (high-grade) glioma WHO grade III or IV. Although the study was not primarily designed as an efficacy evaluation, prolonged survival compared to literature data and response data were observed, which are very rarely seen in this tumor indication. Two patients experienced long-lasting complete tumor remissions. These results implicate targeted TGF-beta2-suppression using AP 12009 as a promising novel approach for malignant gliomas and other highly aggressive, TGF-beta-2-overexpressing tumors.
Subject(s)
Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Glioma/drug therapy , Oligodeoxyribonucleotides, Antisense/therapeutic use , Transforming Growth Factor beta2/genetics , Transforming Growth Factor beta2/metabolism , Adult , Antineoplastic Agents/adverse effects , Antineoplastic Agents/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Glioma/genetics , Glioma/metabolism , Humans , Male , Middle Aged , Oligodeoxyribonucleotides, Antisense/adverse effects , Oligodeoxyribonucleotides, Antisense/genetics , Oligodeoxyribonucleotides, Antisense/metabolism , RecurrenceABSTRACT
OBJECTIVE: Clinically significant intratumoral or peritumoral bleeding from trigeminal nerve tumors is very rare. CLINICAL PRESENTATION: We report the case of a 59-year-old man who presented with recurrent subarachnoid hemorrhage from a left trigeminal nerve malignant peripheral nerve sheath tumor. He presented with decreased consciousness, left facial hypesthesia, and left facial weakness. Trigeminal neuralgia was present for 18 months. Cranial computed tomographic and magnetic resonance imaging scans revealed a left parapontine mass with cystic changes and intratumoral bleeding. Furthermore, signs of hemosiderosis of the subarachnoid space were noted. Lumbar puncture revealed fresh bleeding. Angiography detected no aneurysm or other causes of bleeding. The patient became fully alert within hours, the facial weakness improved within a few days. There was no evidence of vasospasm or persisting hydrocephalus. He underwent left-sided suboccipital craniotomy for macroscopically total tumor removal. INTERVENTION: The patient underwent total tumor removal via a left suboccipital approach. Intraoperatively, evidence of recurrent intratumoral bleeding was noted. Histological examination revealed a malignant peripheral nerve sheath tumor (World Health Organization Grade III). Postoperatively, the hypesthesia improved significantly. The patient was transferred to radiotherapy for external beam radiation. CONCLUSIONS: This is the first report regarding a malignant peripheral nerve sheath tumor of the trigeminal nerve that caused clinically significant subarachnoid hemorrhage caused by intratumoral bleeding.
