Comparison of biological effects of modulated electro-hyperthermia and conventional heat treatment in human lymphoma U937 cells.

Loco-regional hyperthermia treatment has long history in oncology. Modulated electro-hyperthermia (mEHT, trade name: oncothermia) is an emerging curative treatment method in this field due to its highly selective actions. The impedance-matched, capacitive-coupled modulated radiofrequency (RF) current is selectively focused in the malignant cell membrane of the cancer cells. Our objective is studying the cell-death process and comparing the cellular effects of conventional water-bath hyperthermia treatment to mEHT. The U937 human histiocytic lymphoma cell line was used for the experiments. In the case of conventional hyperthermia treatment, cells were immersed in a thermoregulated water bath, whereas in the case of mEHT, the cells were treated using a special RF generator (LabEHY, Oncotherm) and an applicator. The heating dynamics, the maximum temperature reached (42 °C) and the treatment duration (30 min) were exactly the same in both cases. Cell samples were analysed using different flow cytometric methods as well as microarray gene expression assay and western blot analysis was also used to reveal the molecular basis of the induced effects. Definite difference was observed in the biological response to different heat treatments. At 42 °C, only mEHT induced significant apoptotic cell death. The GeneChip analysis revealed a whole cluster of genes, which are highly up-regulated in case of only RF heating, but not in conventional heating. The Fas, c-Jun N-terminal kinases (JNK) and ERK signalling pathway was the dominant factor to induce apoptotic cell death in mEHT, whereas the cell-protective mechanisms dominated in case of conventional heating. This study has clearly shown that conventional hyperthermia and RF mEHT can result in different biological responses at the same temperature. The reason for the difference is the distinct, non-homogenous energy distribution on the cell membrane, which activates cell death-related signalling pathways in mEHT treatment but not in conventional heat treatment.

DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia.

BACKGROUND AND PURPOSE: The electric field and the concomitant heat (electrohyperthermia) can synergistically induce cell death in tumor tissue, due to elevated glycolysis, ion concentration, and permittivity in malignant compared with nonmalignant tissues. Here we studied the mechanism and time course of tumor destruction caused by electrohyperthermia. MATERIAL AND METHODS: Bilateral implants of HT29 colorectal cancer in the femoral regions of Balb/c (nu/nu) mice were treated with a single 30-min shot of modulated, 13.56-MHz, radiofrequency-generated electrohyperthermia (mEHT). Tumors at 0, 1, 4, 8, 14, 24, 48, and 72 h posttreatment were studied for morphology, DNA fragmentation, and cell death response-related protein expression using tissue microarrays, immunohistochemistry, Western immunoblots, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: Modulated EHT treatment induced significant tumor destruction in HT29 xenografts with a peak of a sevenfold increase compared with the untreated controls. The significant treatment-related elevation of DNA fragmentation--detected with TUNEL assay--and apoptotic bodies between 24 and 72 h posttreatment was proof of a programmed cell death response. This was associated with significant mitochondrial accumulation of bax and mitochondrial-to-cytoplasmic release of cytochrome c proteins between 8 and 14 h. Cleaved caspase-3 levels were low and mainly localized to inflammatory cells. The substantial cytoplasmic-to-nuclear translocation of apoptosis-inducing factor (AIF) and its 57-kDa activated fragment detected between 14 and 24 h after treatment indicated AIF as an effector for DNA fragmentation. CONCLUSION: Modulated EHT treatment can induce programmed cell death-related tumor destruction in HT29 colorectal adenocarcinoma xenografts, which dominantly follows a caspase-independent subroutine.

Do field-free electromagnetic potentials play a role in biology?

All bio-systems are imperfect dielectrics. Their general properties however cannot be described by conventional simple electrodynamics; the system is more complex. A central question in our present paper is centered on a controversial debate of the possible effect of the zero fields (only potentials exist). We show that the identical use of the "field-free," "curl-free," and "force-free" terminologies is incorrect, there have definitely different meanings. It is shown that the effective electro-dynamical parameters that describe and modify living systems are the potentials and not the fields. We discuss how the potentials have a role in biological processes even in field-free cases.

Oncothermia treatment of cancer: from the laboratory to clinic.

Oncothermia is a long-time applied method (since 1989) in oncology. Its clinical results excellently show its advantages, however the details of its mechanism are under investigation even today. The method is based on a self-selective process of energy concentration and targets the membrane of the malignant cell, using the temperature gradient and the beta-dispersion of the membrane proteins. To prove the theory we show the experimental evidences in vitro experiments where we showed the definite difference between the conventional heating and the oncothermia at the same temperature. In the next step, we studied some xenograft nude-mice models, verifying the temperature-dependent and non temperature dependent factors. In addition, the synergic effect with some chemotherapies were studied, having more efficacy of the oncothermia with drugs than the conventional heating. These experiments show the definite advantages of the oncothermia compared to its classical counterpart, acting on the same temperature. We have also proved the beneficial effect of oncothermia treatment in the veterinary practice Oncothermia is applied in numerous clinics and hospitals, and we would like to show some characteristic case-reports and also the clinical benefit on the survival time elongation of liver-, pancreas-, brain-, and lung-tumor-lesions.

Effect of curl-free potentials on water.

Living objects are complex systems with various harmonized chemical, thermodynamical, and quantum-mechanical processes in aqueous electrolyte environment. We had studied the effect of curl-free magnetic vector-potential on the matrix of the living matter, on the water. The discussed theoretical considerations are in harmony with the presented simple experiments. It is shown that the vector-potential is actually an effective electro-dynamical parameter which could modify the processes in living systems.

Comparison of echocardiography and gated equilibrium radionuclide ventriculography in the measurements of left ventricular systolic function parameters in healthy dogs.

Left ventricular systolic function was assessed in 12 healthy dogs with equilibrium radionuclide ventriculography. The results of the analysis were compared to traditional echocardiographic measurements. Left ventricular internal dimensions and volume were measured at the time of end-systole and end-diastole. Ejection fraction--one of the most informative parameters of cardiac function--was calculated in each animal. Values (e.g. EDD, ESD, EDV, ESV) measured by the scintigraphic method were significantly (Student's t-test, p < 0.05) higher than the data obtained by echocardiography. Ejection fraction (EF) was the only parameter that did not differ significantly when comparing the two imaging techniques. The difference between the results of parallel measurements was in inverse ratio to the size of the heart.

Oncological scintigraphy in dogs with 99mTechnetium MIBI and DMSA(V)--two case reports.

Oncological scintigraphy is described in two dogs with malignant lymphoma and malignant schwannoma, respectively. The distribution of the radiopharmaceuticals could be visualized for the purpose of detection of neoplasia and eventual metastases, and to evaluate the effectivity of therapy. It is concluded that 99mTechnetium MIBI and 99mTc DMSA (V) scintigraphy is useful for the detection of soft tissue malignancy in dogs.

[Feasibility and accuracy of the combined radioisotope and blue-dye guided sentinel lymph node biopsy in breast cancer]. / A kettós jelöléses órszem nyirokcsomó-biopszia sebészi alkalmazhatósága és pontossága emlórákban.

Sentinel lymph node biopsy is a minimally invasive operation for staging regional lymph nodes in breast cancer. This method was introduced in the last decade. However there are some remaining questions regarding labelling, surgical technique, indications, and the pathological examination of the removed sentinel lymph nodes which have to be answered before can be introduced as the routine clinical practice. 98 patients with primary breast cancer underwent double guided (radioisotope and blue-dye) sentinel lymph node biopsy in our department during a surgical feasibility study between December 1997 and February 2000. The operation was successful in 92 patients (94%). False negative rate, sensitivity and accuracy were 15%, 85% and 95% retrospectively. During the learning curve the success rate improved from 83% to 99%, the sensitivity from 79% to 89% and the accuracy from 88% to 97% and the false negative rate decreased from 21% to 11%. In T1 tumors the false negative rate and accuracy were 6% and 98%, while in T2 tumors these were 24% and 86%. Application of a larger particle sized colloid (200-600 nm), subareolar injection and next day operation technique had no effects on the results. Double guided sentinel lymph node biopsy is a sensitive surgical staging procedure which accurately predicts the lymph node status in T1 breast tumors. The technique used by us is easy to reproduce, and learn and is beneficial in technical and radiation protection aspects.