Principle of heat therapy for tumor treatment Cytotoxic effect of heat therapy ① Heat can induce both apoptosis and cell necrosis, causing cell death. Yan Xin, Department of Gynecology, Anyang Cancer Hospital ②Under the condition of 42 degrees or above, the cell death rate increases exponentially with the increase of heat therapy temperature and the extension of action time. ③Under the condition of 43 degrees or above, the cytotoxic effect of heat therapy still increases, and the time required to kill cancer cells is significantly shortened, keeping 43 degrees for 105 minutes, the survival rate of tumor cells is below one in ten thousand. ④At 70 to 100 degrees, it only takes 0.1 to 0.25 seconds to form coagulative necrosis of cancer cells. ⑤ Heat therapy has sensitizing, potentiating and complementary effects on radiotherapy. ⑥Some chemotherapeutic drugs have increased anti-tumor effects under the effect of heat. Mechanism of killing cancer cells by hyperthermia ① Hyperthermia causes the first damage to cancer cell membranes, while hyperthermia inhibits the synthesis of DNA and RNA and protein, which inhibits the proliferation of cancer cells and leads to cell death. ②High heat increases the activity of lysosomes in cancer cells, and acid hydrolases are released in large quantities, leading to the rupture of the cell membrane, cytoplasmic spillage and cancer cell death. ③ hyperthermia inhibits cancer cell respiration, leading to lactic acid accumulation due to increased anaerobic glycolysis, and the increase in acidity promotes increased enzyme body activity, which eventually leads to cell death. ④ Hyperthermia protects, activates and improves the body’s immune function and enhances the body’s ability to clear cancer cells, which is incomparable to traditional radiotherapy or even surgery. Heat therapy increases the efficacy of radiotherapy Heat therapy increases the local temperature of tumor, accelerates the circulation, increases oxygen saturation, increases oxygen content, increases the cells in sensitive phase, and decreases the lack of oxygen cells in the center of tumor. Heat therapy itself acts in coordination with radiation, heat therapy works before, during and after radiotherapy, and the best efficacy is carried out at the same time, usually after radiotherapy, with temperature less than 42 degrees and time 60 minutes, or after half an hour radiotherapy. Mechanism of radiotherapy + thermotherapy ① S-phase cells, which are insensitive to radiation, are sensitive to heat. Radiation insensitive, M-phase cells sensitive to radiation. Tumors with hypoxia, malnutrition and low PH environment (acidic environment) are insensitive to radiation but sensitive to hyperthermia. Heat therapy interferes with cellular repair and enhances the effect of radiotherapy. ②Tumors are uniformly sensitive to hyperthermia. And the effect of radiotherapy is different depending on the type of tumor tissue and so on. Large tumor volume has good heating effect and high efficacy, and small radiotherapy volume has good efficacy. ③The radiotherapy dose (1/5 to 1/6) and the number of radiotherapy sessions can be reduced after heat therapy without affecting the effect of radiotherapy. ④Radiotherapy can cause immunosuppression, and thermotherapy can activate the immune response. Heat therapy enhances the efficacy of chemotherapy Heat chemotherapy, as one of the comprehensive tumor therapies, is to combine chemotherapy with heat therapy means, to make a scientific and reasonable clinical treatment plan, and to exert the synergistic effect of heat therapy and chemotherapy, in order to improve the survival rate, reduce pain and improve the quality of life. Heat therapy can dilate the blood vessels of tumor tissues, accelerate blood circulation and increase the concentration of chemotherapeutic drugs inside tumor tissues. (41 degrees/60 minutes, blood ECTX increases up to 2 times or more), promoting the approach of drugs to target cells, while heat therapy changes cell permeability, increasing the entry of chemotherapy drugs into cells and enhancing chemotherapy response. Promote the binding of anticancer drugs to cancer cell DNA, such as alkylating agents and platinum drugs, which mainly form covalent bonds with cancer cell DNA molecules, affecting the replication and transcription of cancer cell DNA, and eventually leading to apoptosis of cancer cells. Under the effect of heat, the covalent bonding between drugs and cancer cell DNA is enhanced, achieving effects that cannot be achieved by the original drug dose. It can reduce the side effects and improve the efficacy at the same time. Inhibition of DNA damage repair in cancer cells Polyadenyl diphosphate ribose polymerase (PARP) is a multifunctional enzyme widely found in nucleated cells. When cellular DNA damage occurs, PARP can act as an intracellular molecular receptor that recognizes, binds to, and is activated by DNA breaks. Activated PARP catalyzes the polyADP-ribosylation of histone HI, topoisomerases I and II, DNA polymerase, RNA polymerase, DNA ligase, PARP itself, and many other intranuclear receptor proteins to deliver damage information, trigger the damage response, and ultimately determine the fate of the cell, repairing the damage or apoptosis. The completion of these links requires the participation of ADP-ribosyl and ATP. Heat therapy can reduce the concentration of intracellular ADP and ATP and can reduce the activity of PARP by more than 50%, thus inhibiting the repair of cancer cell DNA to promote death. Reducing and reversing the occurrence of drug resistance in tumor cells Tumor cells are prone to multidrug resistance (MDR) after chemotherapy, which often makes chemotherapy ineffective and fails. Combining chemotherapy with heat can inhibit the expression of P-gp and MRP (denaturing and inactivating them), reverse the multidrug resistance of tumor cells and induce apoptosis. The main chemotherapeutic drugs with heat-enhanced effects are the following The cytotoxicity of drugs increases linearly with increasing temperature: cyclophosphophthalamide, isocyclophthalamide, cetapide, nitrogen mustard; mitomycin, cisplatin, mitoxantrone, etc. The cytotoxicity of drugs is enhanced under certain temperature conditions (domain temperature effect), such as adriamycin, bleomycin and actinomycin, which do not change their cytotoxicity in vitro at temperatures above 37 degrees until the temperature reaches 41-43 degrees when they have a thermally enhanced effect. The cytotoxicity of drugs did not change between 41-43 degrees, such as vincristine and vincristine, which had insignificant thermal effects. Heat therapy can inhibit tumor blood vessel formation and metastatic tendency The formation of blood vessels inside tumors is the basic condition for the growth and development of tumors and metastases. In the early stage, tumor cells are supplied with nutrition through intercellular fluid of adjacent tissues. When the diameter of tumor or metastasis grows to 1-50px, the nutrients provided through microenvironmental infiltration can no longer meet the needs of rapid growth of tumor tissues, and tumors need to establish their own vascular system for further growth and metastasis to occur. The vascular endothelial cells are not as susceptible to mutation as tumor cells, and thus rarely develop drug resistance, and inhibit tumor blood vessel formation and stop tumor growth. The decomposition products of tumor cell degeneration and necrosis after heat therapy can be used as an antigen to stimulate the body’s immune system and produce anti-tumor immune response. When the body temperature rises above 40 degrees (below 42 degrees) the activity of lymphokine-activated killer cells (LAK), the enhanced immune effect of NK cells, T lymphocytes and macrophages, the increased proliferation capacity of lymphocytes, the induction of increased secretion of immunoglobulins from peripheral blood mononuclear cells (PBMC), and the promotion of neutrophil migration and chemotaxis. Protective effect of heat therapy on bone marrow Under the effect of 41.8 degree systemic heat therapy, peripheral blood mononuclear cells secrete granulocyte colony-stimulating factor (G-CSF) and IL-2, IL-6, IL-8, IL-10, TNF-α . G-CSF, IL-2 and IL-6 can directly stimulate the differentiation and maturation of bone marrow hematopoietic cells, etc. Thus, heat therapy can have a protective effect against myelosuppression caused by chemotherapy or radiotherapy. Common deep heat therapy Radiofrequency heat therapy: Contraindications to radiofrequency heat therapy include: 1. patients with intracranial tumors and intracranial hypertension caused by various reasons. 2. patients with more serious cardiovascular disease; those with reduced respiratory function; those with liver and kidney insufficiency. 3. patients with severe anemia or obvious bleeding tendency. 4. patients with recent surgical wounds that have not completely healed. 5. patients with uncontrolled hypertension. As the fifth treatment method for tumor after surgery, radiotherapy, chemotherapy and biological therapy, radiofrequency thermotherapy is called “green therapy” because of its reliable and stable efficacy and small side effects. Surgery, radiotherapy and thermotherapy are all local treatments, but it is better if they are combined with systemic treatment, such as chemotherapy and traditional Chinese medicine. Microwave thermotherapy: Microwave thermotherapy is a new treatment method that uses microwave as the heat source, and through the conduction of special heating device and the blood circulation in the body, the temperature inside the tumor reaches 42.5℃ or more, so as to shrink or eliminate the tumor without damaging the normal tissue. Microwave thermotherapy with radiotherapy/chemotherapy can achieve the effect of increasing efficiency and reducing toxicity. The method is safe and reliable, and patients do not need any invasive preparation. Combined with radiotherapy, it can treat malignant tumors, as well as some benign diseases, such as rheumatoid arthritis, lumbar muscle strain, bronchial asthma, etc. Microwave thermoradiotherapy/chemotherapy is applied to treat gastric cancer, lung cancer, liver cancer, bladder cancer, colon cancer, esophageal cancer, breast cancer, bone tumors and head and neck tumors. Heat therapy treatment twice a week, 48-72 hours apart, 9 times a course of treatment. Heat therapy is administered on the day of chemotherapy administration or the morning of the next day, and twice a week during radiotherapy.