Effect of millimeter wave irradiation on tumor metastasis

One of the major side effects of chemotherapy in cancer treatment is that it can enhance tumor metastasis due to suppression of natural killer (NK) cell activity. The present study was undertaken to examine whether millimeter electromagnetic waves (MMWs) irradiation (42.2 GHz) can inhibit tumor metastasis enhanced by cyclophosphamide (CPA), an anticancer drug. MMWs were produced with a Russian-made YAV-1 generator. Peak SAR and incident power density were measured as 730 +/- 100 W/kg and 36.5 +/- 5 mW/cm(2), respectively. Tumor metastasis was evaluated in C57BL/6 mice, an experimental murine model commonly used for metastatic melanoma. The animals were divided into 5 groups, 10 animals per group. The first group was not given any treatment. The second group was irradiated on the nasal area with MMWs for 30 min. The third group served as a sham control for group 2. The fourth group was given CPA (150 mg/kg body weight, ip) before irradiation. The fifth group served as a sham control for group 4. On day 2, all animals were injected, through a tail vein, with B16F10 melanoma cells, a tumor cell line syngeneic to C57BL/6 mice. Tumor colonies in lungs were counted 2 weeks following inoculation. CPA caused a marked enhancement in tumor metastases (fivefold), which was significantly reduced when CPA-treated animals were irradiated with MMWs. Millimeter waves also increased NK cell activity suppressed by CPA, suggesting that a reduction in tumor metastasis by MMWs is mediated through activation of NK cells.

[1]  C. Korzeniewski,et al.  An enzyme-release assay for natural cytotoxicity. , 1983, Journal of immunological methods.

[2]  Kazuyoshi Takeda,et al.  New aspects of natural-killer-cell surveillance and therapy of cancer , 2002, Nature Reviews Cancer.

[3]  K. Hunter,et al.  Modeling metastasis in vivo. , 2004, Carcinogenesis.

[4]  A Cowan,et al.  Antipruritic effect of millimeter waves in mice: evidence for opioid involvement. , 1998, Life sciences.

[5]  M C Ziskin,et al.  Medical application of millimetre waves. , 1998, QJM : monthly journal of the Association of Physicians.

[6]  M C Ziskin,et al.  Local heating of human skin by millimeter waves: A kinetics study , 2003, Bioelectromagnetics.

[7]  Ziskin Mc,et al.  Electromagnetic millimeter waves increase the duration of anaesthesia caused by ketamine and chloral hydrate in mice , 1997 .

[8]  M C Ziskin,et al.  Effect of millimeter waves on natural killer cell activation , 2005, Bioelectromagnetics.

[9]  I. Puzanov,et al.  Natural killer cell differentiation: insights from knockout and transgenic mouse models and in vitro systems , 1998, Immunological reviews.

[10]  J. Brown,et al.  The effect of cyclophosphamide and other drugs on the incidence of pulmonary metastases in mice. , 1977, Cancer research.

[11]  C. Froelich,et al.  The effect of β-endorphin on natural cytotoxicity and antibody dependent cellular cytotoxicity , 1984 .

[12]  P. Sacerdote,et al.  The opioid antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in BALB/cJ mice. , 2000, Blood.

[13]  C Caux,et al.  Immunobiology of dendritic cells. , 2000, Annual review of immunology.

[14]  G. Page,et al.  Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats , 2001, Pain.

[15]  Y. Iwakura,et al.  Inhibition of B16 melanoma experimental metastasis by interferon‐γ through direct inhibition of cell proliferation and activation of antitumour host mechanisms , 2002, Immunology.

[16]  E.P. Khizhnyak,et al.  Heating patterns in biological tissue phantoms caused by millimeter wave electromagnetic irradiation , 1994, IEEE Transactions on Biomedical Engineering.

[17]  Marvin C. Ziskin,et al.  MILLIMETER WAVES ENHANCE DELAYED-TYPE HYPERSENSITIVITY IN MOUSE SKIN , 1999 .

[18]  Alexis Agelan,et al.  Effect of millimeter waves on cyclophosphamide induced suppression of the immune system , 2002, Bioelectromagnetics.

[19]  L Adorini,et al.  The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. , 1998, Annual review of immunology.

[20]  O. V. Betskiy.  Millimeter waves in biology and medicine : (a review) , 1993 .

[21]  C. Froelich,et al.  Enhancement of natural cytotoxicity by beta-endorphin. , 1983, Journal of immunology.

[22]  N. Tamaoki,et al.  In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. , 1981, Journal of immunology.

[23]  M. Ziskin,et al.  Effect of millimeter waves on cyclophosphamide induced suppression of T cell functions , 2003, Bioelectromagnetics.

[24]  A. Mantovani,et al.  Effect of chemotherapeutic agents on natural cell-mediated cytotoxicity in mice. , 1978, Journal of the National Cancer Institute.

[25]  I. Fidler,et al.  Relationship of host immune status to tumor cell arrest, distribution, and survival in experimental metastasis , 1977, Cancer.

[26]  S. Ben-Eliyahu,et al.  Natural Killer Cell Activity and Resistance to Tumor Metastasis in Prepubescent Rats: Deficient Baselines, but Invulnerability to Stress and β-Adrenergic Stimulation , 2000, Neuroimmunomodulation.

[27]  A Cowan,et al.  Pain relief caused by millimeter waves in mice: results of cold water tail flick tests. , 2000, International journal of radiation biology.

[28]  Sabita Roy,et al.  Evidence for opioid receptors on cells involved in host defense and the immune system , 1998, Journal of Neuroimmunology.

[29]  D. Sarkar,et al.  Chronic Ethanol Inhibits NK Cell Cytolytic Activity: Role of Opioid Peptide β-Endorphin1 , 2001, The Journal of Immunology.

[30]  J. S. McDonald,et al.  Pre-operative versus postoperative administration of morphine: impact on the neuroendocrine, behavioural, and metastatic-enhancing effects of surgery. , 1998, British journal of anaesthesia.

[31]  E. Kedar,et al.  Chemotherapy-induced modulation of natural killer and lymphokine-activated killer cell activity in euthymic and athymic mice , 1994, Cancer Immunology, Immunotherapy.

[32]  A. Pakhomov,et al.  Low-intensity millimeter waves as a novel therapeutic modality , 1999, Digest of Technical Papers. 12th IEEE International Pulsed Power Conference. (Cat. No.99CH36358).

[33]  Marvin C Ziskin,et al.  Combined millimeter wave and cyclophosphamide therapy of an experimental murine melanoma , 2004, Bioelectromagnetics.

[34]  David E. Levy,et al.  Distinct Requirements for IFNs and STAT1 in NK Cell Function1 , 2000, The Journal of Immunology.

[35]  M. Smyth,et al.  Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers , 1999, The Journal of experimental medicine.

[36]  A Cowan,et al.  Hypoalgesic effect of millimeter waves in mice: dependence on the site of exposure. , 2000, Life sciences.

[37]  R. Harris,et al.  Enhancement of natural killer (NK) cell cytotoxicity and induction of NK cell‐derived interferon‐gamma (IFN‐γ) display different kinetics during experimental infection with Trypanosoma cruzi , 2000, Clinical and experimental immunology.

[38]  R. Mandler,et al.  beta-Endorphin augments the cytolytic activity and interferon production of natural killer cells. , 1986, Journal of immunology.

[39]  T. Decker,et al.  A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. , 1988, Journal of immunological methods.

[40]  I. Fidler,et al.  Role of Natural Killer Cells in the Destruction of Circulating Tumor Emboli , 1980 .

[41]  Y. Shinkai,et al.  Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells , 1990, The Journal of experimental medicine.

[42]  N. Saijo,et al.  Analysis of metastatic spread and growth of tumor cells in mice with depressed natural killer activity by anti-asialo GMl antibody or anticancer agents , 2005, Journal of Cancer Research and Clinical Oncology.

[43]  R. Vallejo,et al.  Opioid Therapy and Immunosuppression: A Review , 2004, American journal of therapeutics.