Programmed Cell Death Induced by Modulated Electrohyperthermia

Background. Modulated electrohyperthermia (mEHT) is a noninvasive technique for targeted tumor treatment. Method. HT29 human colorectal carcinoma cell line xenografted to both femoral regions of BalbC/nu/nu mice was treated with a single shot OTM treatment. Histomorphologic, immunohistochemical analysis TUNEL assay, and R&D Apoptosis array were performed on tissue samples. Results. mEHT caused a selective tumor demolition. An upregulation of TRAIL-R2 and FAS was observed. Cleaved caspase-3 positive cells appear at the tumor periphery. Cytochrome c and AIF release was observed in line with massive TUNEL positivity. Conclusion. In HT29 colorectal cancer xenograft, mEHT caused massive caspase independent cell death.

Oncothermia with Chemotherapy in the Patients with Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) is one of the most aggressive and lethal forms of lung cancers. Chemotherapy and radiotherapy would be standard modality for SCLC with median survival being less than 4 months only. Complementary treatment to chemotherapy is desired. Oncothermia will be one of the candidates to this addition. We have made a study of 31 SCLC patients from April 2006 to March 2012. 23 cases were treated with combined chemotherapy and oncothermia, and 8 cases were treated with chemotherapy alone. Three patients from 14 patients (14/31) died in the study period; there were equal numbers in the two arms, including one long survival case of 28 months and one of 26 months, in the combination and chemo-group, respectively .16 patients (16/31) are alive: 4 patients with chemotherapy only, including one long survival case of 28.7 months, and 11 cases with combined therapy including three long survival cases of more than 3 years. We conclude that the combined use of chemotherapy and oncothermia has significantly enhanced the survival rate in comparison with the use of chemotherapy alone (log-rank test: P value < 0.02).

Treatment of Advanced Cervical Cancer with Complex Chemoradio-Hyperthermia

This single arm, retrospective, single institution study investigated intention to treat patients () with advanced cancer of cervix of uterus. The study was performed in 2001–2010, providing 331 sessions. All patients had radiotherapies as fractional radiotherapy and intracavital brachytherapy. Some patients () received chemotherapy (Cisplatin 40 mg/m2/week; concomitantly with tele-radiotherapy) as well. Complementary to the teleradiotherapy, oncothermia was used two times a week, targeting the pelvis. Applied energy dose was 45 W, 60 min. Oncothermia was applied immediately after the infusion, when chemotherapy was also administered. Complete and partial remission were achieved in trimodal therapies for 73.5% of the patients, while we could stabilize the disease for 14.7% of the patients.

Immune Regulation and Oxidative Stress Reduction by Preimplantation Factor following Syngeneic or Allogeneic Bone Marrow Transplantation

Bone marrow transplantation (BMT), a well-established treatment for hematological diseases, is frequently hampered by graft-versus-host disease (GVHD) and/or by infections due to delay in immune restoration. Prelmplantation Factor (PIF) is an embryo-derived peptide whose physiological function is to regulate local and systemic immunity and promote transplant acceptance. Synthetic PIF’s effectiveness to regulate immune response following BMT was herein examined in murine model. PIF administration reduced GVHD following allogenic BMT, decreased skin, liver, and colon inflammation and down regulated GVHD-associated gene expression in the liver. iNOS gene expression was reduced both in liver and colon. In syngeneic BMT, PIF administration reduced proinflammatory genes expression and promoted mice weight recovery up to two months after transplantation. PIF immune-regulatory effects were mediated via interaction with monocytes, resulting in decreased iNOS expression and NO secretion in-vitro. Overall, we demonstrate that by regulating immune response after BMT, PIF reduces inflammation and oxidative stress, leading to transplant success.

New Cancer Paradigm and New Treatment: The Example of METABLOC

Hyperthermia has long been known to interfere with the tumor metabolism. The goal of this paper is to review the potential of metabolic therapy and to suggest that its combination with hyperthermia may be of interest.

“Quo Vadis” Oncologic Hyperthermia?

Hyperthermia was the very first oncotherapy in human medicine based directly on sacral and philosophical roots in ancient cultures. The discovery of electromagnetism gave new hopes a century ago; however, up to now it has been suffering from lack of wide applications. Oncological hyperthermia struggles with multiple technical and medical problems which are far from the complete solution. Technically, the deep heating, the precise focusing, the technical control, and repeatability are challenging. The missing medical explanation of the phenomenon, together with the he missing measurable dose hinders the acceptance of hyperthermia. The contra-feedback of physiology mechanisms makes this method hardly controllable. Multiple, most promising results and studies are mixed together with some negatives and controversial consequences, causing huge fluctuations of its applications. There are positive and negative “believers” of the method, but the decisional facts are missing. A new way gives shape to the development: heating in nanorange, which could solve most of the open problems in oncological hyperthermia.

Oncothermia Research at Preclinical Level

We describe a new electrohyperthermia (oncothermia) method and a tumor treatment system, which was developed to cure companion animals having spontaneously occurring tumors. This dedicated veterinary oncothermia device plays a dual role; this can be a new hope to successfully treat companion animals having tumors. And during these treatments, we can get a large amount of valuable information about the real nature and parameter of the applied electromagnetic field and the behaviour of the tumor under this special modulated radiofrequency field. Then, this experience and knowledge can be transferred directly to the human clinical application to develop more precise treatment systems for human clinical oncology.

Bystander Effect of Oncothermia

Metastatic form of malignant tumor diseases is the most serious problem in oncology and the greatest challenge in tumor therapy. Conventional therapeutical approaches (surgery, irradiation, and chemotherapy) cannot manage this challenge in oncological practice. According to our theory, oncothermia treatment-induced immunogenic tumor cell death can be a very good basis for immunotherapy combination to make systemic tumor control from a local tumor destruction effect. We summarize the molecular basis of the oncothermia treatment-induced immunogenic cell death as a necessary basic condition to achieve the bystander effect.