Language: English | Español

Magnetic Therapy Research: Cancer and Chemotherapy


Static magnetic fields impair angiogenesis and growth of solid tumors in vivo

Strelczyk D, Eichhorn ME, Luedemann S, Brix G, Dellian M, Berghaus A, Strieth S. Walter-Brendel-Center for Experimental Medicine (WBex), Campus Grosshadern, University of Munich (LMU), Munich, Germany.

Exposure to static magnetic fields (SMFs) results in a reduced blood flow in tumor vessels as well as in activation and adherence of platelets. Whether this phenomenon may have a significant functional impact on tumors has not been investigated as yet. The aim of our study was to evaluate the effects of prolonged exposure to SMFs on tumor angiogenesis and growth. Experiments were performed in dorsal skinfold chamber preparations of Syrian Golden hamsters bearing syngenic A-Mel-3 melanomas. On 3 d following tumor cell implantation one group of animals was immobilized and exposed to a SMF of 586 mT for three h. Control animals were immobilized for the same duration without SMF exposure. Using in vivo-fluorescence microscopy the field effects on tumor angiogenesis and microcirculation were analyzed for seven days. Tumor growth was assessed by repeated planimetry of the tumor area during the observation period. Exposure to SMFs resulted in a significant retardation of tumor growth ( approximately 30%). Furthermore, histological analysis showed an increased peri- and intratumoral edema in tumors exposed to SMFs. Analysis of microcirculatory parameters revealed a significant reduction of functional vessel density, vessel diameters and red blood cell velocity in tumors after exposure to SMFs compared to control tumors. These changes reflect retarded vessel maturation by antiangiogenesis. The increased edema after SMF exposure indicates an increased tumor microvessel leakiness possibly enhancing drug-uptake. Hence, SMF therapy appears as a promising new anticancer strategy-as an inhibitor of tumor growth and angiogenesis and as a potential sensitizer to chemotherapy.

Strelczyk D, Eichhorn ME, Luedemann S, Brix G, Dellian M, Berghaus A, Strieth S (September 2009). "Static magnetic fields impair angiogenesis and growth of solid tumors in vivo." Cancer Biology and Therapy. 8 (18):1756-62. PMID: 19633422

Return to top


Static magnetic fields induce blood flow decrease and platelet adherence in tumor microvessels.

Strieth S, Strelczyk D, Eichhorn ME, Dellian M, Luedemann S, Griebel J, Bellemann M, Berghaus A, Brix G. Department of Otorhinolaryngology, University of Munich (LMU), Marchioninistr. 15, Munich 81377 Germany.

Red blood cell flow in capillaries is reduced during exposure to strong static magnetic fields (SMFs). Intratumoral microcirculation is characterized by tortuous microvessels with chaotic architecture and by irregular, sluggish blood flow with unstable rheology. It was the aim of this study to analyze SMF exposure effects on tumor microcirculation with regard to interactions of corpuscular blood components with tumor microvessel walls.

In vivo fluorescence microscopy was performed in A-Mel-3 tumors growing in dorsal skinfold chamber preparations of Syrian Golden hamsters. SMFs with varying field strength (< 600 mT) were generated by changing the distance between a strong NdFeB rod magnet and the tissue region of interest.

Short-time exposure above a magnetic flux density of about 150 mT resulted in a significant reduction of red blood cell velocity (vRBC) and segmental blood flow in tumor microvessels. At the maximum strength of 587 mT, a reversible reduction of vRBC (approximately 40%) and of functional vessel densitiy (approximately 15%) was observed. Prolongation of the exposure time from 1 min to up to 3 h resulted in comparable reductions. Microvessel diameters and leukocyte-endothelial cell interactions remained unaffected by SMF exposure. However, in contrast to tumor-free striated muscle controls, exposure at the maximum flux density induced a significant increase in platelet-endothelial cell adherence in a time-dependent manner that was reversible after reducing SMF strength.

These reversible changes may have implications for functional measurements of tumor microcirculation by MRI and new therapeutic strategies using strong SMFs.

Strieth S, Strelczyk D, Eichhorn ME, Dellian M, Luedemann S, Griebel J, Bellemann M, Berghaus A, Brix G (June 2008). "Static magnetic fields induce blood flow decrease and platelet adherence in tumor microvessels." Cancer Biology & Therapy. 7(6):814-9. PMID: 18340115

Return to top


Effect of magnetic fields on human and rodent cancer cell survival.

Tata, D., Vanhoutten, N., Brook, C., &TrItton T.

In a laboratory study, several rodent and human cancer cell types were exposed to permanent magnetic fields for one hour to determine what percent of the cells would survive compared to unexposed cells. The permanent magnetic field was extremely strong (11.6 Tesla = 116,000 gauss) and was generated by sophisticated equipment. Some of the surviving cell fractions included 25% for human breast carcinoma, 40% for human ovarian carcinoma, and 4% for human mouth carcinoma. Non-Invasive permanent magnetic field modality induces lethal effects on several rodent and human cancers.

In Vitro. Proceedings of the American Association for Cancer Research, 1994; 35, 386.

Return to top


Use of artificial magnetic field for rehabilitation of children with malignant tumors.

Kiselev AV, Grushina TI.

N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Moscow.

Local complications of standard intravenous injections for chemotherapy and due to error of administration were compared in 400 patients (200 of them children) and general wound pathologies described. Treatment for wounds included two modalities: standard medication and alternating or pulsating magnetic field. Magnetic therapy proved highly effective: wound healing was 3-3.5 times faster while duration of treatment--2-3 times shorter than in standard procedure. Clinically-verified partial adhesion-related intestinal obstruction was eliminated by magnetic procedure in 18 children after combined treatment for lymphosarcoma involving the ileum.

Vopr Onkol. 2000;46(4):469-72.

Return to top


Antitumor effect of new local hyperthermia using dextran magnetite complex in hamster tongue carcinoma.

Wada S, Tazawa K, Furuta I, Nagae H.

Department oqf Dentistry and Oral Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.

OBJECTIVE: This study was performed to clarify the usefulness of Dextran magnetite (DM) for the oral cancer hyperthermia.

METHODS: Tumors were induced in golden hamster tongue by 9,10-dimethyl 1-1,2-benzanthracene (DMBA) application. DM suspension was locally injected into the tumor-bearing tongue and tongues were heated up to 43.0-45.0 degrees C, by AC magnetic field of 500 kHz.

RESULTS: The average time taken for the temperature to rise to 43.0 degrees C or above was 162 s (n = 17) at the margin of the tumor and 420 s (n = 17) at the center of the tumor. According to the tumor volume, the time required for an increase in the central temperature of tumor to 43.0 degrees C tended to be prolonged. Both temperatures could be maintained at approximately 43.0-45.0 degrees C for 30 min. The inhibition of the growth of tongue carcinoma in the four-time heating group was significantly greater than in the control group (P < 0.01). Moreover, the survival rate was significantly higher in the heated groups than in the control group (P < 0.01). Histological examination revealed a brown uniform DM accumulation at the stroma in the margin of the tumors. Many of tumor cells disappeared at the site adjacent to this accumulation.

CONCLUSION: These results strongly suggest the usefulness of this local hyperthermic system in the oral region that is accessible to this treatment.

Oral Dis. 2003 Jul;9(4):218-23.

Return to top


Phase I clinical study of a static magnetic field combined with anti-neoplastic chemotherapy in the treatment of human malignancy: initial safety and toxicity data.

Salvatore JR, Harrington J, Kummet T.

Division of Hematology-Oncology, Carl T Hayden VA Medical Center, Phoenix, Arizona 85012, USA.

We have completed the lowest level of exposure in a Phase I study, designed to establish the safety and toxicity of the combination of a static magnetic field (SMF) and antineoplastic chemotherapy in patients with advanced malignancy. The SMF application is carefully controlled by applying the magnet to the patient only in our clinic during chemotherapy administration. No increase in the severity of chemotherapy toxicity as measured by white blood cell count and platelet count was seen in the participants exposed to SMF compared to the historical control subjects. These data have permitted the next group of subjects to be treated at the next dose level. Published 2003 Wiley-Liss, Inc.

Bioelectromagnetics. 2003 Oct;24(7):524-7.

Return to top


Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer.

Zhou PH, Yao LQ, Qin XY, Shen XZ, Liu YS, Lu WY, Yao M.

Zhongshan Hospital, Fudan University, Shanghai 200032, China.

OBJECTIVE: To investigate the effect of magnetic doxorubicin liposome (MDL) in the targeting treatment of nude mice bearing colon cancer.

METHODS: Human colon cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks after the mouse was killed and the tumor was taken out and cut into small pieces to be retransplanted into nude mice so as to establish an experimental model. MDL was prepared by reverse-phase evaporation method. The particle size and structure of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3 groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+) group (magnetic field with the strength of 4 500 G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence spectrophotometry was used to examine the concentrations of DOX in the tissues and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline group (as controls), DOX group, blank liposome group, magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The body weight, longest diameter of tumor, and short diameter vertical to the longest diameter were calculated regularly. The mice were killed 11 days after. The tumors were taken out to undergo staining and light microscopy. Flow cytometry was used to examine the apoptosis of tumor cells.

RESULTS: The particle size of MDL was 230 nm and the magnetic particles (Fe(3)O(4)) were evenly distributed within the liposome. The DOX concentration in tumor tissue of the MDL (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P < 0.05). The DOX concentration in heart and kidney of the DOX group were higher than those of the other 2 groups, and the plasma DOX concentrations of the DOX group was significantly lower than those of the other groups (all P < 0.05). The growth speed of tumor in the MDL (+) group was significantly lower, and the tumor weight was significantly less than in other groups.

CONCLUSION: Magnetic doxorubicin liposome, as a carrier of anticancer drug, has a good targeting function toward the magnetite and has a significant anticancer effect.

Zhonghua Yi Xue Za Zhi. 2003 Dec;83(23):2073-6.

Return to top


Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles.

Ito A, Matsuoka F, Honda H, Kobayashi T.

Department of Biotechnology, School of Engineering, Nagoya University, Nagoya 464-8603, Japan.

Heat shock proteins (HSPs) are recognized as significant participants in immune reactions. We previously reported that expression of HSP70 in response to hyperthermia, produced using our original magnetite cationic liposomes (MCLs), induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by hsp70 gene transfer. A human hsp70 gene mediated by cationic liposomes was injected into a B16 melanoma nodule in C57BL/6 mice in situ. At 24 hours after the injection of the hsp70 gene, MCLs were injected into melanoma nodules in C57BL/6 mice, which were subjected to an alternating magnetic field for 30 minutes. The temperature at the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. The combined treatment strongly arrested tumor growth over a 30-day period, and complete regression of tumors was observed in 30% (3/10) of mice. Systemic antitumor immunity was induced in the cured mice. This study demonstrates that this novel therapeutic strategy combining the use of hsp70 gene therapy and hyperthermia using MCLs may be applicable to patients with advanced malignancies.

Cancer Gene Ther. 2003 Dec; 10(12): 918-25.

Return to top


Investigation on T_c tuned nano particles of magnetic oxides for hyperthermia applications.

Giri J, Ray A, Dasgupta S, Datta D, Bahadur D.

Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Powai, Mumbai-400076, India.

Superparamagnetic as well as fine ferrimagnetic particles such as Fe_{3}O_{4}, have been extensively used in magnetic field induced localized hyperthermia for the treatment of cancer. The magnetic materials with Curie temperature (T_c) between 42 and 50 degrees C, with sufficient biocompatibility are the best candidates for effective treatment such that during therapy it acts as in vivo temperature control switch and thus over heating could be avoided. Ultrafine particles of substituted ferrite Co_{1-a}Zn_{a}Fe_{2}O_{4} and substituted yttrium-iron garnet Y_{3}Fe_{5-x}Al_{x}O_{12} have been prepared through microwave refluxing and citrate-gel route respectively. Single-phase compounds were obtained with particle size below 100 nm. In order to make these magnetic nano particles biocompatible, we have attempted to coat these above said composition by alumina. The coating of alumina was done by hydrolysis method. The coating of hydrous aluminium oxide has been done over the magnetic particles by aging the preformed solid particles in the solution of aluminium sulfate and formamide at elevated temperatures. In vitro study is carried out to verify the innocuousness of coated materials towards cells. In vitro biocompatibility study has been carried out by cell culture method for a period of three days using human WBC cell lines. Study of cell counts and SEM images indicates the cells viability/growth. The in vitro experiments show that the coated materials are biocompatible.

Biomed Mater Eng. 2003;13(4):387-399.

Return to top


Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma.

Ito A, Matsuoka F, Honda H, Kobayashi T.

Department of Biotechnology, School of Engineering, Nagoya University, Nagoya 464-8603, Japan.

Heat shock proteins (HSPs) are recognized as significant participants in cancer immunity. We previously reported that HSP70 expression following hyperthermia using magnetic nanoparticles induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia was conducted using our original magnetite cationic liposomes (MCLs), which have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70) were injected into melanoma nodules in C57BL/6 mice, which were subjected to AMF for 30 min. Temperature within the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% (2/10) of mice. It was also found that systemic antitumor immunity was induced in the cured mice. This study suggests that novel combined therapy using exogenous HSP70 and hyperthermia has great potential in cancer treatment.

Cancer Immunol Immunother. 2004 Jan;53(1):26-32. Epub 2003 Oct 09.

Return to top


Significant differences in the effects of magnetic field exposure on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in two substrains of Sprague-Dawley rats.

Fedrowitz M, Kamino K, Loscher W.

Department of Pharmacology, Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.

We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that power-line frequency (50-Hz) magnetic fields (MFs) at micro T-flux densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF exposure results in an enhanced proliferative activity of the mammary epithelium of SD rats (M. Fedrowitz et al., Cancer Res., 62: 1356-1363, 2002), which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model. However, in contrast with our data, in a similar study conducted by Battelle in the United States, no evidence for a cocarcinogenic or tumor-promoting effect of MF exposure was found in the DMBA model in SD rats (L. E. Anderson et al., Carcinogenesis, 20: 1615-1620, 1999). Probably the most important difference between our and the Battelle studies was the use of different substrains of SD rats; the United States rats were much more susceptible to DMBA than the rats used in our studies. This prompted us to compare different substrains of SD outbred rats in our laboratory in respect to MF effects on cell proliferation in the mammary gland, susceptibility to DMBA-induced mammary cancer, and MF effects on mammary tumor development and growth in the DMBA model. The SD substrain (termed "SD1") used in all of our previous studies was considered MF-sensitive and used for comparison with another substrain ("SD2") obtained from the same breeder. In contrast with SD1 rats, no enhanced cell proliferation was determined after MF exposure in SD2 rats. MF exposure significantly increased mammary tumor development and growth in SD1 but not SD2 rats. These data indicate that the genetic background plays a pivotal role in effects of MF exposure. Different strains or substrains of rats may serve to evaluate the genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure.

Cancer Res. 2004 Jan 1;64(1):243-51.

Return to top


Hepatocellular Carcinoma: Regional Therapy with a Magnetic Targeted Carrier Bound to Doxorubicin in a Dual MR Imaging / Conventional Angiography Suite--Initial Experience with Four Patients.

Wilson MW, Kerlan RK Jr, Fidelman NA, Venook AP, LaBerge JM, Koda J, Gordon RL.

Departments of Radiology and Medicine, University of California, San Francisco, 505 Parnassus Avenue, Room M-361, San Francisco, CA 94143.

Four patients with inoperable hepatocellular carcinoma were treated with a magnetic targeted carrier bound to doxorubicin (MTC-DOX) by using a joint magnetic resonance (MR) imaging/conventional angiography system consisting of a 1.5-T short-bore magnet connected to a C-arm angiography unit by a sliding tabletop. Selective transcatheter delivery of the MTC-DOX to the hepatic artery was monitored by using intraprocedural MR imaging, and interim catheter manipulation was performed with fluoroscopic guidance to optimize agent delivery to the tumor and minimize delivery to normal tissue. The final fraction of treated tumor volume ranged from 0.64 to 0.91. The fraction of affected normal liver volume ranged from 0.07 to 0.30. The dual MR imaging/conventional angiography system shows promise for directing magnetically targeted tumor therapies. Copyright RSNA, 2004

Radiology. 2004 Jan;230(1):287-93.

Return to top


Principles of magnetodynamic chemotherapy.

Babincova M, Leszczynska D, Sourivong P, Babinec P, Leszczynski J.

Department of Biophysics and Chemical Physics, Comenius University, Mlynska dolina F1, Bratislava 842 48, Slovakia.

Basic principles of a novel method of cancer treatment are explained. Method is based on the thermal activation of an inactive prodrug encapsulated in magnetoliposomes via Neel and Brown effects of inductive heating of subdomain superparamagnetic particles to sufficiently high temperatures. This principle may be combined with targeted drug delivery (using constant magnetic field) and controlled release (using high-frequency magnetic field) of an activated drug entrapped in magnetoliposomes. Using this method drug may be applied very selectively in the particular site of organism and this procedure may be repeated several times using e.g. stealth magnetoliposomes which are circulating in a blood-stream for several days. Moreover the magnetoliposomes concentrated by external constant magnetic field in tumor vasculature may lead to embolic lesions and necrosis of a tumor body and further the heat produced for thermal activation of a drug enhances the effect of chemotherapy by local hyperthermic treatment of neoplastic cells.

Med Hypotheses. 2004 Mar;62(3):375-7.

Return to top


Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet.

Nobuto H, Sugita T, Kubo T, Shimose S, Yasunaga Y, Murakami T, Ochi M.

Department of Orthopedic Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

The development of an active drug delivery system is an attractive approach to increase the targetability of anticancer agents. In the present study, we examined the efficiency of systemic chemotherapy with small magnetic liposomes containing doxorubicin (magnetic DOX liposomes) and an externally applied electromagnetic force in osteosarcoma-bearing hamsters. Syrian male hamsters inoculated with osteosarcoma, OS515, in the limb were studied 7 days after inoculation. The efficiency of this system was evaluated by measuring the tissue distribution and tumor-suppressing effects of DOX on primary tumor growth and lung metastases. A DC dipole electromagnet was used, and the hamster's tumor-bearing limb was placed between 2 poles after the i.v. administration of liposomes. The dose of DOX and the magnetic field strength were fixed at 5 mg/kg and 0.4 T, respectively. Administration of magnetic DOX liposomes followed by 60 min application of magnetic field produced a 3- to 4-fold higher maximum DOX concentration in the tumor. This newly designed systemic chemotherapy significantly suppressed primary tumor growth for at least 2 weeks, though other DOX treatments also suppressed compared to control. Histologic examination confirmed a greater antitumor effect of this systemic chemotherapy compared to standard methods. In addition, this approach significantly suppressed lung metastases measured at 3 weeks posttreatment. These results suggest that this systemic chemotherapy can effectively reduce primary tumor growth and suppress lung metastasis due to increased targeting of DOX. Such targeted drug delivery for anticancer agents would provide clinical advantages compared to current methods. Copyright 2004 Wiley-Liss, Inc.

Int J Cancer. 2004 Apr 20;109(4):627-35.

Return to top