Apoptosis in selective antitumor therapy in various human malignancies

Loefflmann, A.

Institute for Cancer Research and Treatment, Neuhauserstr. 25 /III, Munich, Germany

An oxygen evolving enzyme Mr 67 kDalton derived from photosystem of green plants ( MDA) used in combination with proteins Mr 62, 43 and 13,8 k Dalton (PI) is able to reverse malignancy by inducing apoptosis. The initial step of targeted disruption of malignancy is hemorrhagic necrosis. Studies have shown that this combined therapy plays an important role as DNA damaging biochemotherapeutic agents in chemically induced fibrosarcomas in Wistar rats and various human malignant growths. After simultaneous intravenous injection of MDA and PI nuclear DNA degradation and mitochondrial DNA fragmentation of malignant cells is seen. The subsequent dose-dependent activation of all lymphocyte subclasses indicates in our view a significant relationship between removal of the debris of hemorrhagic necrosis and systemic lymphatic activation. Since December 1993 we have treated a patient with multiple lung metastases after removal of the right kidney and both suprarenal glands in a preclinical trial because of hypernephroma; a second patient with inoperable adenocarcinoma of the right lower lung has been treated since March 1995 with selective antitumor therapy. Due to selective destruction of malignant cells we obtained an increase in general biomarkers such as glutamatdehydrogenase (GLDH) as parameter for the selective degradation of mitochondria and uric acid for the destruction of DNA. As individual markers for the destruction of the membranes of the malignant cells were measured increased values of tumor markers CA 15-3 and TPA. Clinical response consisted in swelling of lung metastases, intermittend pain, coughing and expelling fragments of necrotic tissue through the trachea. The underlying physiological principle behind the strategy involves the molecular basis of recognition and destruction of tumor targets.

Loefflmann, A., European Patent No.04232623, 19.01.94. / Loefflmann, A., United States Patent No. 5,516,754, May 14, 1996

LOCATION DATE TIME
Lecture Hall II Wednesday, April 8 10:40 am