Chemotherapy Combined With Hyperthermia Los Angeles
Hyperthermia significantly enhances the cytotoxicity of various anticancer drugs to get better clinical results.
Chemotherapy (also called chemo) is a type of cancer treatment that uses drugs to destroy cancer cells. Chemotherapy works by stopping or slowing the growth of cancer cells, which grow and divide quickly. It can also harm healthy cells that divide quickly, such as those that line your mouth and intestines or cause your hair to grow. Damage to healthy cells may cause side effects. Often, side effects get better or go away after chemotherapy is over.
Possible Benefit of Hyperthermia combined with Chemotherapy:
The most obvious benefit of hyperthermia to chemotherapy is the fact that hyperthermia shows synergy with some drugs against cancer cells. It is of importance that hyperthermia appears to strengthen not just one but several drugs belonging to more than just one class of chemo-therapeutic agent.
Several studies have investigated the relationship between hyperthermia and its effects on normal tissue, in animals as well as humans. Although the topic has by no means been exhaustively studied, it appears that hyperthermia has more effect on tumor tissue than on normal tissue. This lack of significant host toxicity should allow for the inclusion of hyperthermia in chemotherapeutic regimens without significant additional detrimental effect to the patient.
Tumors are well known to often become clinically resistant or refractory to a given chemotherapeutic drug regimen. Too frequently, the development of tumor resistance to one drug will also lower the likelihood of obtaining a therapeutic response to other drugs. Hyperthermia may be helpful in either preventing or delaying the development of tumor resistance to a given chemotherapy drug or in reversing the acquired resistance of a tumor to a given chemotherapeutic drug.
Apoptosis (programed cell death):
The combination of chemotherapy with hyperthermia strenghtens the cytotoxic effects of the anti-tumor drugs by inducing apoptosis (programmed cell death). Well know publishing scientist, Kameda and others, have reported that apoptosis was significantly enhanced when mild hyperthermia was combined with an anti-tumor drug
Repair Inhibition of sub-lethal damage:
Hyperthermia was found to inhibit the repair of DNA damage by anti-tumor drugs and radiation and increased the anti-tumor activity of chemotherapy and radiotherapy. Cancer cells that are received sub-lethal damage from radiation or chemotherapy attempt to repair the damage but hyperthermia can make this repair ineffective which causes the death of the cancer cells.
Additional Mechanisms of Hyperthermia and Chemotherapy combined:
- Acceleration of primary mode of action (alkylating reaction, protein damage, oxygen-radicals, DNA-strand breaks)
- Increased intracellular drug concentration (drug uptake, membrane damage, protein damage, pH changes)
Critical Reviews in Oncology/Hematology 43 (2002) 33–56
Molecular effects of hyperthermia
- Cell membrane, cytoskeleton
- Changes in fluidity/stability of cell membrane
- Changes in cell shape
- Impaired transmembranal transport
- Changes in membrane potential
- Modulation of transmembranal efflux pumps (MDR)
- Apoptosis induction
- Intracellular proteins
- Impairment of protein synthesis
- Protein denaturation
- Aggregation of proteins at the nuclear matrix
- Induction of HSP-synthesis
- Nucleic acids
- Impairment of RNA/DNA synthesis
- Inhibition of repair enzymes
- Altered DNA conformation
- Other alterations of cell function
- Intracellular metabolism of other substrates
- Gene expression, signal transduction
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