Effects of hyperthermia in a malignant tumor

Abstract

The mechanisms of immediate and delayed tumor cell killing by hyperthermia were investigated in EMT-6 neoplasms implanted in BALB/cKa mice. Radiofrequency electromagnetic fields were used to achieve a curative local dose of 44 degrees C for 30 minutes. The tumors were sampled sequentially, during and after heat therapy, and studied by light and elecron microscopy. Assays for cell survival, including cell cultures, were performed at various times after completion of therapy. Focal cytoplasmic swelling, rupture of the plasma membrane and peripheral migration of heterochromatin were observed 5 minutes after initiation of therapy and led to cytoplasmic fragmentation by the end of the treatment period (30 minutes). Necrosis of most cells occurred 2--6 hours after the end of treatment. At 48 hours, there were no recognizable tumor cells. A scar replaced the tumor bed 14 days later. Viable (clonogenic) tumor cells were still 2% of control levels at the end of therapy and then progressively decreased to 0.0003% at 48 hours, confirming the morphologic observations and indicating that factors other than the direct effect of heat on tumor cells contributed to complete tumor eradication. Our findings, coupled with previous studies, suggest that the immediate heat induced necrosis in this tumor occurs through the mechanisms of physical changes in the plasma membrane. The delayed (post-therapy) cell death is likely due to modifications in the environment of the tumor bed.

The impact of hyperthermic chemotherapy on human gastric cancer cell lines: Preliminary results

“…Most previous reports of morphological studies of cell death induced by chemotherapy and thermotherapy have referred only to 'necrosis' (23). Several studies have shown that apoptosis is the major mode of cell death induced by hyperthermia and anti-cancer drugs such as CDDP (4,9,20,(24)(25)(26).…”

Numerical Analysis of Dielectric Heating in Cancerous Liver Tissue

“…Rising temperatures have been shown to change cell membrane fluidity and permeability, and this causes dysfunction of actin filaments and microtubules, leading to impairment of facilitated diffusion across the cell membrane. 16 This process was first thought to be the main cause of hyperthermiainduced cell death. However, mitochondrial dysfunction has been shown to occur with heat-induced injury.…”

Dynamic computed tomography predicts tumor temperature and response to thermoradiotherapy in superficial and subsurface tumors

“…16 Hyperthermia in the tumor causes focal cytoplas- mic swelling, rupture of the plasma membrane, peripheral migration of heterochromatin, and, subsequently, cytoplasmic fragmentation and necrosis. 17 However, hyperthermia also causes damage to blood vessels. Even a temperature (e.g., 42°C) that increases blood flow in normal tissues can easily reduce tumor blood flow.…”