Frequency Of Tumor-specific Research Articles

Search for tumor-specific frequencies of amplitude-modulated 27 MHz electromagnetic fields in mice with hepatocarcinoma xenografted tumors

Aim: The Pasche research group has reported that tumor-specific electromagnetic field frequencies have physiological and potential anti-tumor effects in cells, animals, and humans. Our aim was to investigate whether these fields have similar effects on physiological parameters in murine tumor models.Methods: Human HuH7 or HEPG2 cells were implanted in the right flank of 8-week-old female RAG gamma 2 C immunodeficient mice. An oximeter was used to record systolic blood pressure (pulse) in free-roaming conscious mice. Mice pulses were recorded and analyzed using a in-house software that also controlled the low-frequency generator for modulating the 27.12 MHz carrier wave at selected frequencies.Results: We performed exposures using both systematic scans at low frequencies and at the pre-determined frequencies reported by the Pasche group as altering both pulse and tumor growth in humans. Those exposures produced no detectable change in physiological parameters of tumor-bearing mice.Conclusion: No tumor-related frequencies were found, neither using systematic scans of frequencies nor published specific frequencies. There might obviously be differences between animal and human models, but our approach did not confirm the physiological data of the human Pasche group data.

Frequency, Cause, and Awareness of Pulmonary Embolism in Oncologic Patients

The frequency of pulmonary embolism (PE) in oncologic patients ranges from 1.1 % to 7.3 % depending on whether not only symptomatic findings but also incidental and initially overseen events are considered. The frequency of PE is tumor-specific. Most frequently PE occurs in patients with malignancy of the ovary (25 %), pancreas, brain, uterus, and multiple myeloma. Most rarely is PE found in patients with malignancy of the testis (< 1 %).The tumor-specific frequency shows that the association of malignancy and PE is not equally true for alle malignancies. A number of arguments that support the above association are also valid in non-oncologic patients.The awareness of the diagnosing radiologist and the thrombus mass decide whether or not an unexpected PE is detected. An increased awareness is suggested in patients with malignancies with high PE frequency and in patients with advanced oncologic disease.

Frequency, cause, and awareness of pulmonary embolism in oncologic patients

The frequency of pulmonary embolism (PE) in oncologic patients ranges from 1.1 % to 7.3 % depending on whether not only symptomatic findings but also incidental and initially overseen events are considered. The frequency of PE is tumor-specific. Most frequently PE occurs in patients with malignancy of the ovary (25 %), pancreas, brain, uterus, and multiple myeloma. Most rarely is PE found in patients with malignancy of the testis.The tumor-specific frequency shows that the association of malignancy and PE is not equally true for alle malignancies. A number of arguments that support the above association are also valid in non-oncologic patients.The awareness of the diagnosing radiologist and the thrombus mass decide whether or not an unexpected PE is detected. An increased awareness is suggested in patients with malignancies with high PE frequency and in patients with advanced oncologic disease.

The anti-proliferative effects of RF EMF amplitude-modulated at tumor specific frequencies and mediation by calcium.

11079 Background: Experimental and clinical evidence shows that whole body administration of low-level radiofrequency electromagnetic fields, amplitude-modulated (AM RF EMF) at specific frequencies...

Targeted treatment of cancer with radiofrequency electromagnetic fields amplitude-modulated at tumor-specific frequencies

In the past century, there have been many attempts to treat cancer with low levels of electric and magnetic fields. We have developed noninvasive biofeedback examination devices and techniques and discovered that patients with the same tumor type exhibit biofeedback responses to the same, precise frequencies. Intrabuccal administration of 27.12 MHz radiofrequency (RF) electromagnetic fields (EMF), which are amplitude-modulated at tumor-specific frequencies, results in long-term objective responses in patients with cancer and is not associated with any significant adverse effects. Intrabuccal administration allows for therapeutic delivery of very low and safe levels of EMF throughout the body as exemplified by responses observed in the femur, liver, adrenal glands, and lungs. In vitro studies have demonstrated that tumor-specific frequencies identified in patients with various forms of cancer are capable of blocking the growth of tumor cells in a tissue- and tumor-specific fashion. Current experimental evidence suggests that tumor-specific modulation frequencies regulate the expression of genes involved in migration and invasion and disrupt the mitotic spindle. This novel targeted treatment approach is emerging as an appealing therapeutic option for patients with advanced cancer given its excellent tolerability. Dissection of the molecular mechanisms accounting for the anti-cancer effects of tumor-specific modulation frequencies is likely to lead to the discovery of novel pathways in cancer.

Abstract 916A: Cancer cell proliferation is inhibited by specific modulation frequencies

Abstract Background: Hepatocellular carcinoma (HCC), a leading cause of cancer death worldwide, now has the fastest growing rate in the United States. The intrabuccal administration of amplitude modulated electromagnetic fields (AM-EMF) is a novel, minimally invasive treatment modality. There is clinical evidence that this novel treatment approach elicits therapeutic responses in patients with cancer (1, 2). However, there is no known mechanism explaining the anti-proliferative effect of very low intensity electromagnetic fields. Methods: Hepatocellular carcinoma cells were exposed to 27.12 MHz radiofrequency electromagnetic fields using in vitro exposure systems designed to replicate in vivo conditions. Cancer cells were exposed to tumor-specific modulation frequencies, previously identified by biofeedback methods in patients with a diagnosis of cancer. Control modulation frequencies consisted of randomly-chosen modulation frequencies within the same 100 Hz to 21 kHz range as cancer-specific frequencies. Growth inhibition was evaluated by measuring tritiated thymidine incorporation. RNA-Seq was used to identify genes with differential expression in cells exposed to HCC-specific AM-EMF. Confocal laser scanning microscopy allowed the visualization of the mitotic spindle. Karyotype assessment compared HepG2 receiving HCC-specific AM-EMF to those not receiving exposure. Results: The growth of hepatocellular carcinoma and breast cancer cells was significantly decreased by hepatocellular carcinoma-specific and breast cancer-specific modulation frequencies, respectively. However, the same frequencies did not affect proliferation of nonmalignant hepatocytes or breast epithelial cells. Inhibition of hepatocellular carcinoma cell proliferation was associated with downregulation of XCL2 and PLP2. Furthermore, hepatocellular carcinoma-specific modulation frequencies disrupted the mitotic spindle. Karyotype analysis was unrevealing. Conclusion: These findings uncover a novel mechanism controlling the growth of cancer cells at specific modulation frequencies without affecting normal tissues, which may have broad implications in oncology. Reference List (1) Barbault A, Costa F, Bottger B, Munden R, Bomholt F, Kuster N, et al. Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach. Journal of Experimental &amp; Clinical Cancer Research 2009;28:51. (2) Costa FP, de Oliveira AC, Meirelles R, Machado MCC, Zanesco T, Surjan R, et al. Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields. Br J Cancer 2011;105:640-8. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 916A. doi:1538-7445.AM2012-916A

Phase II study of intrabuccally-administered amplitude-modulated electromagnetic fields in patients with advanced hepatocellular carcinoma

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.

Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach

PurposeBecause in vitro studies suggest that low levels of electromagnetic fields may modify cancer cell growth, we hypothesized that systemic delivery of a combination of tumor-specific frequencies may have a therapeutic effect. We undertook this study to identify tumor-specific frequencies and test the feasibility of administering such frequencies to patients with advanced cancer.Patients and methodsWe examined patients with various types of cancer using a noninvasive biofeedback method to identify tumor-specific frequencies. We offered compassionate treatment to some patients with advanced cancer and limited therapeutic options.ResultsWe examined a total of 163 patients with a diagnosis of cancer and identified a total of 1524 frequencies ranging from 0.1 Hz to 114 kHz. Most frequencies (57–92%) were specific for a single tumor type. Compassionate treatment with tumor-specific frequencies was offered to 28 patients. Three patients experienced grade 1 fatigue during or immediately after treatment. There were no NCI grade 2, 3 or 4 toxicities. Thirteen patients were evaluable for response. One patient with hormone-refractory breast cancer metastatic to the adrenal gland and bones had a complete response lasting 11 months. One patient with hormone-refractory breast cancer metastatic to liver and bones had a partial response lasting 13.5 months. Four patients had stable disease lasting for +34.1 months (thyroid cancer metastatic to lung), 5.1 months (non-small cell lung cancer), 4.1 months (pancreatic cancer metastatic to liver) and 4.0 months (leiomyosarcoma metastatic to liver).ConclusionCancer-related frequencies appear to be tumor-specific and treatment with tumor-specific frequencies is feasible, well tolerated and may have biological efficacy in patients with advanced cancer.Trial registrationclinicaltrials.gov identifier NCT00805337

Combined L-/T-Type Calcium Channel Blockers

Opening of the voltage-dependent Ca2+ channels permits influx of Ca2+ across the plasma membrane, triggering diverse physiological processes. These channels are widely distributed in the cardiovascular system, constituting the main route for Ca2+ entry essential for excitation and contraction. Ten unique α1 subunits, grouped in 3 families (CaV1, CaV2, and CaV3), that encode the low-voltage–activated T-type and the high-voltage–activated L-, N-, P/Q- and R-type Ca2+ channels, have been identified.1,2 L-type Ca2+ channels are predominantly expressed in the hearts and peripheral vasculature and serve as the preferred molecular target of the initial Ca2+ channel antagonists in the treatment of hypertension.3 Recently, a growing body of evidence has accumulated depicting important roles of T-type Ca2+ channels in the regulation of cardiovascular function, such as generation of pacemaker potential and regulation of arterial resistance.3,4 T-type Ca2+ channels are found in various cell types, including neurons, cardiomyocytes, vascular smooth muscle cells, and endocrine cells, where they participate in a variety of physiological processes, such as low-threshold Ca2+ spike generation, action potential firing, pacemaking, impulse conduction, maintenance of myogenic tone, cell proliferation, and hormone secretion.1 In addition to their predominant role in the regulation of vascular function, T-type Ca2+ channels are also involved in cardiomyocyte growth and survival.3 T-type Ca2+ channel blockers are capable of interrupting certain pathological hypertrophic signaling pathways, including calcineurin-mediated nuclear factor of activated T cells–3 activation.1 The importance of voltage-dependent Ca2+ channels is demonstrated by the clinical efficacy of Ca2+ channels blockers in certain disease conditions, as well as the widespread distribution and function of these channels.1 Three classes of chemically distinct L-type Ca2+ channel blockers have been widely used clinically depending on their biophysical and conformation-dependent interactions …

A phase II study of amplitude-modulated electromagnetic fields in the treatment of advanced hepatocellular carcinoma (HCC)

15155 Background: Phase I data show that low levels of electromagnetic fields modulated at specific frequencies administered intrabucally with the THERABIONIC device are a safe and potentially effective treatment for advanced cancer. The device emits a 27.12 MHz radiofrequency signal, amplitude-modulated at tumor-specific frequencies ranging from 0.2 to 23,000 Hz. The device is connected to a spoon- like coupler placed in the patient’s mouth during treatment. Patients with advanced HCC and limited therapeutic options were offered treatment with HCC-specific frequencies. Methods: From October 2005 to October 2006, 38 patients with advanced HCC were recruited in a phase II study. The patients received three daily 40 min treatments until disease progression or death. The median age was 64.0 ± 14.2 years. 32 patients were male and 29 patients had documented progression of disease (POD) by IV contrast imaging prior to study entry. 8 patients had not received prior therapy because of metastases (3), poor medical condition (3), declined chemotherapy (2). Results: As of January 2007, 12 patients are still on therapy, 20 patients died of tumor progression, 2 patients are lost to follow-up and 3 patients withdrew consent. 27 patients are eligible for response. The overall objective response rate as defined by partial response (PR) or stable disease (SD) in patients with prior documented POD was 31.6%: 3 PR and 9 SD. The median survival was 20.7 weeks with a median duration of therapy of 17.5 weeks. 13 patients have received therapy for more than six months. The median duration of response is 12.9 weeks. 12 patients reported pain at study entry: 8 of them (66%) experienced decreased pain during treatment. There were no NCI grade 2/3/4 toxicities. One patient had grade 1 mucositis and grade 1 fatigue. Conclusion: In patients with advanced HCC, THERABIONIC is a safe and effective novel therapeutic option, which has significant anti-tumor effect and provides pain relief in the majority of patients. [Table: see text] No significant financial relationships to disclose.

Functional tumor reactive T cells in bone marrow and blood of pancreatic cancer patients

4113 Background: Memory T-cells specifically reactive to tumor antigens should be an ideal source to generate therapeutic effector cells against pancreatic cancer. To our knowledge functionally active, specific memory T-cells have not been demonstrated in pancreatic cancer patients. To investigate if functional memory T-cells are present in the bone marrow (BM) of pancreatic cancer patients, we performed in vitro stimulation with tumor associated antigens presented by autologous dendritic cells (DC). Methods: DC and T-cells were generated in a 14-day culture with GM-CSF and IL-4 (DC) and/or IL-2, IL-4, IL-7 (TC) from BM derived CD34+ progenitor cells of 35 patients with pancreatic carcinoma and chronic pancreatitis. DC were pulsed with lysate from autologous tumor cells, Muc I peptide - fragments and PBMCs (peripheral blood mononuclear cells as negative controls). Tumor specific T-cell response was evaluated in a single-cell interferon-γ-, IL4-, IL10- and IL12- release immunospot assay (Elispot). Cytotoxicity of CD8+ T-cells against primary cultured tumor cells was measured by a functional DNA-release, and trypan-blue staining assay. Results: In the individual patient, T-cells stimulated by tumor lysate pulsed DC as well as DC pulsed with Muc I peptide showed a significantly higher response in the INF-γ Elispot assay compared with T-cells stimulated by PBMC-lysate pulsed DC. The tumor specific T-cell frequency found in the bone marrow was consistently high (49/105 to 109/105) in all patients compared with the response found in the periferal blood (9/105 to 53/105; p<0,05 to p<0,001). In the cytotoxicity assay, the response was significantly higher when T-cells were stimulated with tumor lysate pulsed DC compared with PBMC-lysate pulsed DC. Conclusions: Our data indicate for the first time a regular occurrence of tumor antigen specific T cell responses during the course of pancreatic cancer that lead to the generation and enrichment of functional tumor cell-reactive memory T cells in the bone marrow. The BM may therefore be considered an important lymphoid organ for the induction or maintenance of anti tumor immune responses in pancreatic cancer. No significant financial relationships to disclose.