A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients.

Background: Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy. Methods: In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient's signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study. Results: Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients' lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates. Conclusion: PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.

Targeted Delivery of Anticancer Drug Loaded Charged PLGA Polymeric Nanoparticles Using Electrostatic Field.

Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg-1 ] versus DLNs-based chemotherapy [0.75 mg kg-1 ]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.

High-Frequency (30 MHz-6 GHz) Breast Tissue Characterization Stabilized by Suction Force for Intraoperative Tumor Margin Assessment.

A gigahertz (GHz) range antenna formed by a coaxial probe has been applied for sensing cancerous breast lesions in the scanning platform with the assistance of a suction tube. The sensor structure was a planar central layer and a metallic sheath of size of 3 cm2 connected to a network analyzer (keySight FieldFox N9918A) with operational bandwidth up to 26.5 GHz. Cancer tumor cells have significantly higher water content (as a dipolar molecule) than normal breast cells, changing their polarization responses and dielectric losses to incoming GHz-based stimulation. Principal component analysis named S11, related to the dispersion ratio of the input signal, is used as a parameter to identify malignant tumor cells in a mouse model (in vivo) and tumor specimens of breast cancer patients (in vitro) (both central and marginal parts). The results showed that S11 values in the frequency range from 5 to 6 GHz were significantly higher in cancer-involved breast lesions. Histopathological analysis was the gold standard for achieving the S11 calibration to distinguish normal from cancerous lesions. Our calibration on tumor specimens presented 82% positive predictive value (PPV), 100% negative predictive value (NPV), and 86% accuracy. Our goal is to apply this system as an in vivo non-invasive tumor margin scanner after further investigations in the future.

Positive electrostatic therapy of metastatic tumors: selective induction of apoptosis in cancer cells by pure charges.

BACKGROUND: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. METHODS: We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples. RESULTS: Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC-based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative-associated proteins (Ki67, CD31, and HIF-1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real-time polymerase chain reaction results demonstrate up/down-regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues. CONCLUSION: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy-treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.

The design and fabrication of nanoengineered platinum needles with laser welded carbon nanotubes (CNTs) for the electrochemical biosensing of cancer lymph nodes.

A new biosensor for detecting cancer involved sentinel lymph nodes has been developed via the electrochemical tracing of fatty acid oxidation as a distinct metabolism of malignant cells invading lymph nodes (LNs). The system included integrated platinum needle electrodes that were decorated by carbon nanotubes (as hydrophobic agents) through laser-assisted nanowelding. It was applied to record the dielectric spectroscopy data from LN contents via electrochemical impedance spectroscopy. The system was applied for dielectric spectroscopy of LN contents via electrochemical impedance approach. The reduced lipid content of involved LNs, due to fat metabolism by invasive cancer cells, would decrease the charge transfer resistance (RCT) of the LNs with respect to their normal counterparts. Multi-walled carbon nanotubes (MWCNTs) with superhydrophobic properties were used to enhance the interaction of Pt needle electrodes with the lipidic contents of lymph nodes. This is the first time that a fatty acid metabolism-based sensing approach has been introduced to detect involved LNs. Moreover, a novel electrode decorating method was applied to enhance the interfacial contact of this lipid detection probe (LDP). In order to avoid doubt about the biocompatibility of ferrocyanide, [Fe(CN)6]4- and ferricyanide, [Fe(CN)6]3-, a biocompatible injectable metal ion-based material, ferric carboxymaltose, was selected and applied as the electrolyte for the first time. Rabbit LNs were tested using the LDP in the animal model phase. The system was then used in vitro on 122 dissected human LNs in the operating room. Calibration of the results showed an excellent match between the dielectric response of the LDP (known as charge transfer resistance (RCT)) and the final pathological diagnoses. The LDP may have a promising future after further clinical investigations for intra-operative distinction between normal and cancerous LNs.

Capture-free deactivation of CTCs in the bloodstream; a metastasis suppression method by electrostatic stimulation of the peripheral blood.

While limited investigations have been reported on CTC elimination and its profits, recently, some new works were reported on detection followed by the destruction of CTCs. Limitations and complications of CTC capturing procedures have highly reduced the chance of selective destruction of CTCs in the bloodstream in the therapeutic guidelines of the patients. Here, we selectively deactivated the invasive function of CTCs during their circulation in the bloodstream by exposing the whole blood to pure positive electrostatic charge stimulation (PPECS). Our treatment suppressed pulmonary metastasis and extended the survival of the mice had been intravenously injected by electrostatically deactivated 4T1 breast cancer CTCs. Moreover, the number of cancerous lung nodules was drastically reduced in the mice injected by treated CTCs in comparison with the non-treated cohort. Evaluating the side effect of the PPECS on the blood components revealed no major effect on the functional properties of the white blood cells, and just a negligible fraction (∼10%) was damaged during this process. This approach does not need any capturing or targeting of CTCs from the blood as it is focused on perturbing the electrical function of negatively-charged tumor cells after being exposed to positive electrostatic charges. Taken together, continuous in-vivo deactivation of CTCs by PPECS with no requirement to complicated capturing protocols may improve the survival of cancer patients.