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.

Fourty-three cases of systemic amyloidosis were identified in an unselected autopsy series from our institute (6305 autopsies between 1979 and 1993) and classified immunohistochemically by means of a panel of antisera directed against five major amyloid fibril proteins. Amyloid A (AA) amyloidosis was the most common type, being found in 21 cases (48.8%). Transthyretin-derived (ATTR) amyloidosis was present in 11 cases (25.6%), and immunoglobulin light chain-derived (AL) amyloidosis in 10 cases (23.3%). A single case (2.3%) contained deposits of more than one type of systemic amyloid. AA amyloidosis was associated with chronic inflammatory or infectious diseases (81%), malignant tumours (19%) or both (9.5%). Immunoglobulin light chain-derived amyloidoses were associated with myeloma (50%) or primary (idiopathic; 50%). In AA and AL amyloidosis the kidney was the organ most frequently involved. ATTR amyloid affecting mostly the heart and lungs presented as senile systemic amyloidosis. Systemic amyloidosis was the cause of death in 5 cases (12%) and caused symptoms in 17 cases (39%). Our results suggest that most cases can be classified by using a panel of sensitive and specific antibodies against five major amyloid fibril proteins. This technique may make amyloid type-specific therapy possible for AL amyloid patients who do not have evidence of an underlying plasma cell dyscrasia.

This interdisciplinary, individually tailored and function-preserving treatment procedure has proven to be a well-tolerated therapeutic option in cases with refractory orbital RMS. It provides both improvement of local tumor control and quality of life.

Perioperative fractionated IMBT after extensive but vision-preserving tumor resection seems to be a safe and well-tolerated treatment of advanced/recurrent malignancies involving the skull base. These preliminary data suggest that combined operation and perioperative fractionated IMBT is a palliative therapeutic option in the management of fatal malignancies involving the base of the skull, a strategy which leaves the patients' visual acuity intact.

Several studies have recently demonstrated that human gliomas express Fas, Fas ligand (FasL), Bcl-2 and TGFbeta2 at some degree. These factors are considered to interact with apoptotic processes and to have immuno-reactive potential. Their role for tumor evasion from the immune surveillance is currently under examination. To date, there is only limited information about the definite expression patterns of these four factors in human gliomas, particularly in pilocytic astrocytoma (PA) and recurrent tumors. We analyzed 75 human gliomas for the immunohistochemical expression of Fas, FasL, Bcl-2, and TGFbeta2: (1) 25 PAs (WHO grade I), (2) 25 primary glioblastomas (WHO grade IV), and (3) 25 paired initial and recurrent glioblastomas (WHO grade IV), respectively. Co-expression of all four factors was present in the majority of specimens, i.e. in 72% (18/25) of PAs and 88% (47/50) of primary glioblastomas. Pilocytic astrocytomas showed significantly higher scores of TGFbeta2 expression (p < 0.05) and significantly lower Fas, Fas ligand and Bcl-2 scores (p < 0.05) than glioblastomas. There were no significant expression differences in initial versus recurrent glioblastoma specimens. Likewise, no significant correlation was observed between protein expression and clinical parameters, i.e. total survival time or progression free survival time, as documented by Kaplan-Meier method and log rank-test. In conclusion, Fas, FasL, Bcl-2 and TGFbeta2 are differently expressed in PAs versus glioblastomas. These factors, however, are not associated with patient prognosis. The broad co-expression of these factors may enable new therapeutic approaches in the future.