Tumours

F: Daudert, physician in Bad Aibiling at Rosenheim: Second International Congress for Energy Medicine in Seefeld 1998. People with the following criteria were used for this study: advanced cancer, people who had exhausted the usual resources of traditional medicine and people with greatly reduced immune competent cells (less than 50%). More than 300 patients with epithelial tumors were divided into two groups and treated one of the two groups additionally with PEMF. The treatment was otherwise identical for both groups (vitamin and mineral infusions, immune stimulation, oxygen flooding therapy). The treatment was administered for a period of two weeks with a repetition after three months. Blood tests, which were analysed by an independent clinical laboratory, yielded comparable values between the two groups. It was found that the buildup of the immune system could be significantly accelerated with PEMF.

Biological effects of PEMF (pulsing electromagnetic field): an attempt to modify cell resistance to anticancer agents.
Pulsing Electromagnetic Field (PEMF) effects lead to a modification of the multidrug resistance (MDR) of cells in vitro and in vivo.

The murine leukemic doxorubicin-resistant cell line, P388/Dx, subjected to PEMF irradiation in vitro, showed a significant difference in thymidine incorporation when the concentration of doxorubicin reached a level of 1 microgram/mL, which corresponds to the inhibition dose 50 (ID50). The human lymphoblastic leukemia vinblastine-resistant cell line, CEM/VLB100, also showed a significant modification under the same experimental conditions at the in vitro ID50 corresponding to a vinblastine concentration of 100 ng/mL.

BDF1 mice transplanted with P388/Dx cells also had an increase in their life span when doxorubicin was injected intraperitoneally in fractionated doses, while being subjected to PEMF irradiation.

Pasquinelli, P., J Environ Pathol Toxicol Oncol 1993 Oct-Dec;12(4):193-7

Input - 220VAC 50/60 Hz 1 Kw Fuse 6 amps
Output - Complex (0.3-250 MHz) pulse train
Average field power - 60 watts
Pulse width - <1 microsecond
Pulse repetition rate - 2-5 pulses per second
Applicator (probe) - 15 cm diameter indiction coil
Average induced voltage - 18 volts within 8 cm
Body Penetration - 15cm at ful power
Attenuation - 1 /D3(D = distance)
Overall dimensions - 44.5"h, 21.5"w, 20"d
Net weight - Approx. 150 lb (68 Kilo)
Mounting - Four 3" castor wheels
Treatment timer - 5 minutes max
Ventilation - Chassis fan
Interference suppression EMI shielded
NOTE: Ozone produced in plasma chamber must be vented to outside with - 2" dia. flexible hose.

USAGE

Simplicity of usage is a major feature of the IMI, as magnetic pulses pass through all matter except certain metals. The applicator probe is held flat against the clothing or skin of the area to be treated, and the start button pressed. The device will begin emitting several popping noises per second (from the arc in the plasma chamber that initiates each pulse) until the 5-minute treatment timer turns it off. if desired, or if the probe is moved to another location, the start button will initiate another 5minute operation for up to four cycles, depending on the treatment protocol for a particular clinical condition.

It is noted that in over 100,000 IMI treatments for a variety of medical problems, no adverse effects or incidents have been reported in patients or in technicians exposed to IMI pulses for many hundreds of hours a year.

THEORY OF OPERATION

Normal Cells

All of the many types of living cells that make up the tissues and organs of the body are tiny electrochemical units. They are powered by a "battery* that is continually recharged by the cells' metabolic chemistry in a closed loop of biological energy.

We are concerned here with that battery, which consists of the membrane that surrounds the cell. The electrical charge, or voltage across the membrane of a normal, healthy cell varies from about 70 to 100 millivolts; this is called the Transmembrane Potential, or TIVIP.

When a cell is poisoned, damaged, deprived of nutrients or infected, energy is lost in fighting the problem and the TIVIP falls to a level where the cell loses its vitality and either struggles to heal itself or dies.

Medical literature over the past few decades offers ample proof that the induction of tiny currents of electricity is remarkably effective in healing, regenerating and revitalizing cells damaged by trauma. Many of the earlier techniques developed from this research involved implanting fine electrodes at the boundaries of the injured tissue, and causing a tiny current to flow through the affected area from low-voltage batteries. Subsequently, it was found that these healing currents could also be induced by relatively weak magnetic devices placed close to the trauma and kept there for days or weeks.

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Thus the healing effects of microcurrents generated or induced in the conductive pathways of the body have been well established and this application is an accepted clinical procedure.

There remained for Professor Pappas to discover that a weak pulsed magnetic field, hundreds of times faster than had ever been used, applied for a millionth of a second at a time within a frequency spectrum never before used in medical devices, could accomplish much more within a few minutes what other stronger magnetic induction devices required days or weeks to affect--and to do so with much more efficient and far-reaching therapeutic results.

In short, the IMI is capable of raising the TMP of sick or damaged cells into a normal range, thus restoring their bioenergy, facilitating the exchange of potassium and sodium ions (the Na/K pump) and restoring their normal rate of production of ATP which fuels the entire process. Normal healthy cells are not adversely affected by IMI because, as in recharging any battery, the membrane-batteries of living cells in particularly will not accept an overcharge.

Let us consider the action of the IMI in electrical terms. The massive surge of current circulating in the applicator loop, which acts as an antenna, generates a field of complex radiofrequency energy energy that is "broadcast" outward in all directions normal to the direction of current flow in the loop. The quickly expanding and collapsing pulse of magnetic energy easily penetrates biological tissues. When a changing magnetic field intersects a conductor in a closed circuit, it generates a current in the conductor; this is the basic principle on which all rotary electric generators and alternators operate. The expanding and contracting magnetic component of the pulse causes current to flow in the many conductive paths of the body, including nerve fibers, blood vessels (blood serum is electrically conductive) and the fluid bathing the cells.

As the magnetic field expands through the living tissue, it induces electron flow, or current in one direction; as it collapses, the direction is reversed. Electrons always flow from negative (cathode) to positive (anode) potential.

The membrane itself is a dielectric that could be compared to a capacitor. Its electrical charge is positive on the outer surface, negative on the inner surface. Therefore such induced current polarized to push ions toward the positive outside of the cell membrane are blocked just as no current will flow when the positive terminals of two batteries are connected together.

Conversely, current flowing away from the membrane will pull electrons away from it, and cause more electrons or negative ions to pile up on its interior surface, thus incrementally increasing the charge, or potential across the membrane and driving the TMP up towards a normal, healthy value for that cell.

This is one reason why the IMI is so quick and effective in helping damaged cells heal. Also, although it produces no heat in the tissue, for reasons that cannot yet be presented here it appears to increase the blood circulation around damaged tissue. This is important, as increasing the supplies of nutrients is also an effective aid to cell repair; this is particularly true in trauma where circulation has been impaired by crushed or severed blood vessels or the inflarnation and swelling that compress capillaries, blocking flow to both the injured and uninjured cells.

Put in terms of physical chemistry, rather than biological terms, another parallel phenomenon appears to occur: the acceleration of adencisine triphosphate (ATP) synthesis and other aspects of the cell's biochemical anabolism. The electrons drawn to the inner membrane by elevating the TMP increase the ionic charge in the interior. This raises the internal degrees of freedom at a molecular level, catalyzing dormant biochemical reactions that would not otherwise proceed as quickly due to lack of available energy. Entropy is reduced and the cell's metabolic rate increased, enabling the cell to heal itself and attain an optimum functional level.

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Cancer Cells

Cancer cells grow faster, divide and multiply much more rapidly than normal cells. As with all living cells, once their TMP falls into a critical low value, mitosis is triggered and the cell divides into two identical copies. When the magnetic induction action of the IMI prevents a drop in the TMP to that critical mitosis-trigger level, the fastgrowing cancer cell cannot divide and continues to grow larger until death occcurs.

It is clear that as a cancer cell grows at an uncontrolled rate without dividing, the membrane is stretched thinner and thinner. When the ratio of volume to surface area becomes too large, the membrane is unable to absorb enough nutrients to support the bulk of the cell and starvation will result in cell death.

There are several theories about what happens to bring about cell death under these conditions; some or all of these may apply to different types of cancer cells.

Soft, harmless, electromagnetic treatment of cancer is quite new to medical science, and there are still new facts to be discovered. But research continues as new tools are developed to explore phenomena at the microscopic levels of the molecule and the cell.

Bjorn Nordenstrom, a predminent Swedish scientist has found that cells of cancers he has successfully treated with electrotherapy appear to become dehydrated and die. He used an invasive surgical procedure, implanting electrodes in the tumor to generate the microcurrents that the IMI appears to create non-invasively by magnetic induction. His basic techniques were adopted in China where, from 1988 to 1993 over 4,000 cases of advanced malignancy were treated. Of 2516 carcinoma cases in patients over 50 years old, a 78% favorable response rate was reported.

Dr. C.K. Chou, an American cancer researcher and his colleagues have found that these same microcurrents alter the pH of the cancer cell and alter its DNA so that it cannot reproduce.

In the special cases of HIV and hepatitis infections, repeated experiments have shown that when the infected blood is treated in vitro with 50 to 100 microamperes of current, it appears to be virtually free of these viruses. This is an exciting discovery as it suggests that the same phenomenon may occur in the body ana raises the possibility that when an IMI device can be designed large and powerful enough to scan or cover tne whole body in a single treatment, these and perhaps other viral infections could be successfully conquered.

Another important aspect of the thinning membrane of a growing cancer cell is that it becomes more porous. This appears to have two significant results. Anticancer antibodies of the immune system can more easily penetrate the membrane to attack the cell. Also, when electromagnetic fields are applied to the cancer, a phenomenon known as Electroporosis develops; this permits certain pharmaceuticals that have proven effective in chemotherapy to penetrate the membrane more quickly and easily--allowing a significant reduction in the dosage of chemicals that may have harmful side effects.

 

Bjorn Nordenstrom, a predminent Swedish scientist has found that cells of cancers he has successfully treated with electrotherapy appear to become dehydrated and die. He used an invasive surgical procedure, implanting electrodes in the tumor to generate the microcurrents that the IMI appears to create non-invasively by magnetic induction. His basic techniques were adopted in China where, from 1988 to 1993 over 4,000 cases of advanced malignancy were treated. Of 2516 carcinoma cases in patients over 50 years old, a 78% favorable response rate was reported.

Dr. C.K. Chou, an American cancer researcher and his colleagues have found that these same microcurrents alter the pH of the cancer cell and alter its DNA so that it cannot reproduce.

Cancer & Chemotherapy
Effect of magnetic fields on human and rodent cancer cell survival
Use of artificial magnetic field for rehabilitation of children with malignant tumors
Antitumor effect: local hyperthermia using dextran magnetite complex in hamster tongue carcinoma
Clinical study of static magnetic field combined with anti-neoplastic chemotherapy in treatment of human malignancy
Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer
Heat shock protein gene therapy combined with hyperthermia using magnetic nanoparticles
Investigation on Tc tuned nano particles of magnetic oxides for hyperthermia applications
Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles
Significant differences in the effects of magnetic field exposure on mammary carcinogenesis in rats
Regional Therapy with a Magnetic Targeted Carrier Bound to Doxorubicin
Principles of magnetodynamic chemotherapy
Systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet


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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.


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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.


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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. swada-tym@umin.ac.jp

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.


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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. joseph.salvatore@med.va.gov

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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.

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