Therapeutic effect of heat shock on T-cell lymphoma in inbred Sprague-Dawley rat.
Anticancer effect of heat shock, either alone or in combination with the drug PMEDAP, and cold water immersion stress were studied in an in vivo model of s.c. transplanted rat T-cell lymphomas in an inbred Sprague-Dawley rat line (SD/cub). Significant anticancer effect was induced by repeated sessions of heat shock; decrease of s.c. lymphoma weight and prolongation of survival time of treated rats was found to be dependent on the number of HS sessions. Much stronger therapeutic effect was observed after repeated heat shock in combination with PMEDAP administration. Light and electron microscopy studies were performed to characterize the alterations within the lymphomas. Morphologically, cellular alterations corresponding with apoptosis were observed in lymphoma cells after repeated heat shock. Indirect immunoperoxidase technique was used to detect HSP 72/73 protein(s), p53 and Bcl2 proteins in lymphomas heated directly or indirectly. The induction of HSP 72/73 protein(s) was found in the lymphoma tissues from autopsied animals exposed to heat shock; the intensity of its expression was dependent on the experimental design. The expression of p53 and BcL2 proteins was not changed in lymphoma cells of HS treated animals as compared to that of untreated lymphoma bearing controls; the Bcl2 protein was present in both treated and untreated lymphomas, and the p53 protein remained undetectable in all samples. Contrary to the heat shock, the cold stress did not suppress growth of lymphomas and, furthermore, accelerated the infiltration of parenchymatous organs with lymphoma cells.
Otová
B
B
Institute of Biology, 1st Medical Faculty, Charles University, Prague, Czech Republic. boto@LF1.cuni.cz
Mráz
M
M
Mandys
V
V
Panczak
A
A
Schramlová
J
J
Votruba
I
I
Holy
A
A
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis; D001835:Body Weight; D003131:Combined Modality Therapy; D017679:Cryotherapy; D005260:Female; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis; D006979:Hyperthermia, Induced; D007101:Immersion; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D009386:Neoplastic Syndromes, Hereditary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000964:Antimetabolites, Antineoplastic; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C059499:9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine; D000225:Adenine