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
Meningeal melanocytoma refers to the uncommon clinical appearance of a generally benign tumour deriving from leptomeningeal melanocytes. Meningeal spread of this tumour is very rarely observed. We present the case of a 38-year-old man with meningeal melanocytoma of the cerebello-pontine angle, who showed a biphasic course of this disease, with a stable period followed by a steady progress within few months. After surgical resection of the melancytoma in the left skull base and of a first local recurrence five years later, a second local recurrence occurred 6 years after diagnosis, with intracerebral and spinal meningeal seeding. This tumor did not respond to a combined radiochemotherapy including oral temozolomide, and the patient died 5 months after starting treatment for this relapse. Secondary malignisation of the melancytoma is suggested.
