Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies.

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.

Intracerebral and intrathecal infusion of the TGF-beta 2-specific antisense phosphorothioate oligonucleotide AP 12009 in rabbits and primates: toxicology and safety.

Here, we provide first evidence that long-term continuous infusion of highly purified antisense phosphorothioate oligodeoxynucleotides (S-ODN) into brain parenchyma is well tolerated and thus highly suitable for in vivo application. AP 12009 is an S-ODN for the therapy of malignant glioma. It is directed against human transforming growth factor-beta (TGF-beta2) mRNA.

Pharmacological effects of oral enzyme combinations.

Combinations of hydrolytic enzymes have been used for therapy of variety of diseases for a long time, their pharmacology, however, is being recognized only in the course of last decades. In the article, the following pharmacological effects of combinations of oral hydrolytic enzymes are reviewed: fibrinolytic, hemorheologic, anti-edematous, anti-inflammatory, activation of macrophages and NK cells, modulation of adhesion molecules, cytokines and immune complexes. Pharmacological effects are classified on four levels: biochemical, physiological, medical, and immunological.

The intestinal absorption of orally administered hydrolytic enzymes and their effects in the treatment of acute herpes zoster as compared with those of oral acyclovir therapy.

Oral enzymes are known as therapy of herpes zoster for more than 30 years. Nevertheless, today's standard treatment of herpes zoster in immunocompetent patients is oral acyclovir. Other therapies are no longer customary because of their insufficient efficacy and frequent side effects.

[The favorable effect of hydrolytic enzymes in the treatment of immunocytomas and plasmacytomas].

At present attention is focused on research of biomodulating influences on tumorous processes, in particular inhibition of metastatic spread of tumors. In the aetiopathogenesis an important part is played by immune complexes, interaction of cytokines. The authors tested the supporting effect of hydrolytic enzymes in plasmocytoma and immunocytoma.

The use of hydrolytic enzymes as adjuvant therapy in AIDS/ARC/LAS patients.

The purpose of this paper is to discuss a hypothesis corroborating the use of hydrolytic enzymes in AIDS/ARC/LAS patients, showing high levels of circulating immune complexes (CIC). Other diseases, revealing high CIC-levels as well, may be improved or even cured by eliminating CIC. The results obtained from experiences of CIC-elimination by hydrolytic enzymes are presented below.

Purification and properties of a low molecular weight DNA polymerase from Neurospora crassa.

A third DNA polymerase 'C' with low molecular weight was isolated and purified 3700-fold from ground hyphae of Neurospora crassa WT 74 A, which shows similarities to beta- and gamma-polymerases from higher eukaryotes: preference for poly(rA)(dT) as a template/primer, inhibition by p-chloromercuribenzoate, resistance against N-ethylmaleimide up to 10 mmol/l, and molecular weight of about 40000. This polymerase elutes as a distinct peak from DEAE-cellulose at 0.60 mol/l KCl and has an optimum for K+ at 2-20 mmol/l, for Mn2+ at 0.