HYPERTHERMIA AS A TRIGGER FOR ACTIVATION OF HORMETIC MECHANISMS

Failing in the cure of cancer sometimes by conventional treatment methods points us to make new approaches besides these conventional methods. Using hyperthermia which effects angiogenesis and cancer stem cells, combination with chemotherapy, radiotherapy and gene therapy is seen as a method that can help the treatment of cancer.

Bulletin of the New York Academy of Medicine

Hyperthermia refers to elevation tumor temperature from 39 up to 43 degree Celsius. Actually Therapeutic Hyperthermia has been used as an adjuvant treatment for cancer, since end of the 19th century after observations William Coley who found that tumor is diminished after induction of fever by bacterial toxins. Hyperthermia therapy refers to treatment tumors through heating which has been used since the time of the ancient Egyptians. The term ‘Hyperthermia’ in oncology means treatment of malignant disease by heating in different ways. Hyperthermia is usually applied as an adjuvant therapy method in combination with other modalities such as Radiotherapy or Chemotherapy in cancer treatment. Typically there are three categories for Hyperthermia, including local, regional and whole body. Based on the temperature Whole body hyperthermia classify in 3 type, mild, fever range and extreme. In Mild hyperthermia, the temperature is from 37.5 up to 38.5 degree Celsius, in fever range hyperthermia, 38.5 up to 40 degree Celsius, and extreme hyperthermia, the temperature above 40 degree Celsius. Now Days Whole body hyperthermia known as immunotherapy related to cancer treatment in oncology. Here we will review whole body hyperthermia related to cancer treatment.

Biorheology, 1984

Differences in blood perfusion rates between turrors and nornal tissue can be utilized to selectively heat many solid turrors. Bl=d flow in nornal tissues is considerably increased at temperatures comm:mly applied during localized hyperthermia. In contrast, turror blood flow may respond to localized heat typically in two different blood flow patterns: Flow may either decrease continuously with increasing exposure t:iJre and/or tenperature or flow may exhibit a transient increase followed by a decline. A decrease in blood flow at high thernal doses can be observed in llDst of the turrors, whereas an increase in flow at low thernal doses seems to occur less frequently. The inhibition of blood flow at high thernal doses may lead to physiological changes in the microenvirorurent of the cancer cells that increase the cell killing effect of hyperthermia. Flow increases at low thernal doses can enhance the efficiency of other treatment llDdalities, such as irradiation or the administration of antiproliferate drugs.

Current Cancer Treatment - Novel Beyond Conventional Approaches, 2011

Tumori

Hyperthermia, the heating of tumors to 41.5-43 degrees C, could be today considered the fourth pillar of the treatment of cancer. Employed for 20 years in Europe, the U.S.A. and Asia, hyperthermia, used in addition to radiotherapy, chemotherapy and surgery, increases both local control and overall survival, restores the chance of the surgery for inoperable tumors and allows a new low-dosage treatment of relapsed cancers previously treated with high radiotherapy dosage without increasing toxicity. Hyperthermia can be either superficial, produced by a microwave generator, or regional, produced by a radiofrequency applicator with multiple antennas, which emanate a deep focalized or interstitial heating. The results are confirmed by phase III randomized trials, with level 1 evidence. A review of the international literature on hyperthermia, the experience of the University Hospital of Verona Radiotherapy Department (Italy) and a summary of the Symposium regarding the Evolution of Clinic...

The Lancet Oncology, 2002

European Journal of Cancer and Clinical Oncology, 1983

HAR-KEDAR, BLEEHEN NM. Experimental and clinical aspects of hyperthermia applied to the treatment of cancer. In: LEE JT, ADLER H, eds. Advances in RadiationBiology.

International Journal of Radiation Oncology*Biology*Physics, 1991

Inherent cellular radiosensitivity in vitro has been shown to be a good predictor of human tumor response in viva In contrast, the importance of the intrinsic thermosensitivity of normal and neoplastic human cells as a factor in the responsiveness of human tumors to adjuvant hyperthermia has never been analyzed systematically. A comparison of thermal sensitivity and thermo-radiosensitization in four rodent and eight human-derived cell lines was made in vitro. Arrhenius plots indicated that the rodent cells were more sensitive to heat killing than the human, and the break-point was 0.5"C higher for the human than rodent cells. The relationship between thermal sensitivity and the interaction of heat with X rays at low doses was documented by thermal enhancement ratios (TER's). Cells received either a 1 hr exposure to 43°C or a 20 minute treatment at 45°C before exposure to 300 kVp X rays. Thermal enhancement ratios ranged from 1.0 to 2.7 for human cells heated at 43°C and from 2.1 to 5.3 for heat exposures at 45°C. Thermal enhancement ratios for rodent cells were generally 2 to 3 times higher than for human cells, because of the fact that the greater thermosensitivity of rodent cells results in a greater enhancement of radiation damage. Intrinsic thermosensitivity of human cells has relevance to the concept of thermal dose; intrinsic thermo-radiosensitization of a range of different tumor cells is useful in documenting the interactive effects of radiation combined with heat. Hyperthermia, Thermo-radiosensitization, Human carcinoma cells, Arrhenius plots, Thermal enhancement ratio, Rodent cells.

Current Neurovascular Research, 2004

Although brain metabolism consumes high amounts of energy and is accompanied by intense heat production, brain temperature is usually considered a stable, tightly regulated homeostatic parameter. Current animal research, however, has shown that different forms of functional neural activation are accompanied by relatively large brain hyperthermia (2-3°C), which has an intra-brain origin; cerebral circulation plays a crucial role in dissipating this potentially dangerous metabolic heat from brain tissue. Brain hyperthermia, therefore, reflects enhanced brain metabolism and is a normal physiological phenomenon that can be enhanced by interaction with common elements of an organism's environment. There are, however, instances when brain hyperthermia becomes pathological. Both exposure to extreme environmental heat and intense physical activity in a hot, humid environment restrict heat dissipation from the brain and may push brain temperatures to the limits of physiological functions, resulting in acute life-threatening complications and destructive effects on neural cells and functions of the brain as a whole. Brain hyperthermia may also result from metabolic activation induced by various addictive drugs, such as heroin, cocaine, and meth-amphetamine (METH). In contrast to heroin and cocaine, whose stimulatory effects on brain metabolism invert with increases in dose, METH increases brain metabolism dosedependently and diminishes heat dissipation because of peripheral vasoconstriction. The thermogenic effects of this drug, moreover, are enhanced during physiological activation, resulting in pathological brain hyperthermia. Since brain hyperthermia exacerbates drug-induced toxicity and is destructive to neural cells, uncontrollable use of amphetamine-like drugs under conditions restricting heat dissipation from the brain may result both in acute lifethreatening complications and clinically latent but dangerous morphological and functional brain destruction.