[Hypoxia in malignant tumors the target for clostridial therapeutic gene strategies].
In the fast proliferating malignant tumors which are characterized by abnormal vascularisation develop non oxidized regions of a low oxygen partial pressure (pO2). Because these tumors are unsusceptible to a conventional therapy they were chosen for clostridial therapeutic gene strategies. There were presented different strategies using clostridia as selective vectors of destructive genes, e.g. cytosine deaminase and nitroreductase activating in reduced microenvironment of tumors--nonactive prodrugs towards strong cytostatics, destroying hypoxic tumor cells. In general, they form a basis for CDEPT strategy (clostridial-directed enzyme prodrug therapy) and moreover in connection with antivessel cytostatic they form COBALT strategy (combination bacteriolytic therapy). In another strategy genetically modified clostridia are transferred to the gene of TNF alpha cytokine which production regulates fractionated ionizing radiation activating a promoter include in the clostridial vector. Sat last, there were discussed new problems connected with clostridial therapeutic gene strategies.
Wallner
Grzegorz
G
II Katedra i Klinika Chirurgii Ogólnej Akademii Medycznej, Lublinie. wallner@panaceum.am.lublin.pl
Misiuna
Paweł
P
Cygan
Wiesław
W
Cygan
Zygmunt
Z
D015687:Cell Hypoxia; D003013:Clostridium; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha