Effect of Post IORT Wound Fluid Secretion (PIWFS) on the Behavior of Breast Cancer Cells: Stimulator or Inhibitor; Report of an Experimental Study on Breast Cancer.

BACKGROUND: Although investigating the probable side effects of post intraoperative radiotherapy wound fluid secretion (PIWFS) is crucial, especially in clinical cases, no report has been published on the effect of PIWFS on the remaining tumor cells (in the vital state) in cavity side margins or surrounding regions. These tumor cells might be directly/indirectly exposed to intraoperative radiation therapy (IORT). Here, for the first time, we investigated the effect of PIWFS on tumor cells of the same patient extracted from the excised tumor in the spheroid form. METHODS: We generated 8 human-derived breast tumor spheroids from 4 patient specimens who received to IORT, dissociated and cultured them in microfluidic devices. The spheroids from each sample were treated with the patients' PIWFS and DMEM medium separately. Two different parameters, called area and number of detached cells (NDCs), were determined and investigated to evaluate the spheroids' vital and proliferative states. RESULTS: The results showed severe transformation in tumor spheroids' function into more invasive and proliferative functions after treatment with PIWFS. CONCLUSION: Although the radiation-induced bystander effect may have a role in this observation, further experiments must be done to better clarify the probable desired or non-desired effects of post-IORT secretion for both the remaining tumor cells and the surrounding immune cells.

Myeloid-derived suppressor cells (MDSCs) in brain cancer: challenges and therapeutic strategies.

The most fatal malignancy of the central nervous system (CNS) is glioblastoma. Brain cancer is a 'cold' tumor because of fewer immunoregulatory cells and more immunosuppressive cells. Due to the cold nature of brain cancers, conventional treatments which are used to manage glioma patients show little effectiveness. Glioma patients even showed resistance to immune checkpoint blockade (ICB) and no significant efficacy. It has been shown that myeloid-derived suppressor cells (MDSCs) account for approximately 30-50% of the tumor mass in glioma. This study aimed to review MDSC function in brain cancer, as well as possible treatments and related challenges. In brain cancer and glioma, several differences in the context of MDSCs have been reported, including disagreements about the MDSC subtype that has the most inhibitory function in the brain, or inhibitory function of regulatory B cells (Bregs). There are also serious challenges in treating glioma patients. In addition to the cold nature of glioma, there are reports of an increase in MDSCs following conventional chemotherapy treatments. As a result, targeting MDSCs in combination with other therapies, such as ICB, is essential, and recent studies with the combination therapy approach have shown promising therapeutic effects in brain cancer.

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.

A label-free graphene-based impedimetric biosensor for real-time tracing of the cytokine storm in blood serum; suitable for screening COVID-19 patients.

Concurrent with the pandemic announcement of SARS-CoV-2 infection by the WHO, a variety of reports were published confirming the cytokine storm as the most mortal effect of the virus on the infected patients. Hence, cytokine storm as an evidenced consequence in most of the COVID-19 patients could offer a promising opportunity to use blood as a disease progression marker. Here, we have developed a rapid electrochemical impedance spectroscopy (EIS) sensor for quantifying the overall immune activity of the patients. Since during the cytokine storm many types of cytokines are elevated in the blood, there is no need for specific detection of a single type of cytokine and the collective behavior is just measured without any electrode functionalization. The sensor includes a monolayer graphene on a copper substrate as the working electrode (WE) which is able to distinguish between the early and severe stage of the infected patients. The charge transfer resistance (R CT) in the moderate and severe cases varies about 65% and 138% compared to the normal groups, respectively and a specificity of 77% and sensitivity of 100% based on ELISA results were achieved. The outcomes demonstrate a significant correlation between the total mass of the three main hypercytokinemia associated cytokines including IL-6, TNF-α and IFN-γ in patients and the R CT values. As an extra application, the biosensor's capability for diagnosis of COVID-19 patients was tested and a sensitivity of 92% and specificity of 50% were obtained compared to the RT-PCR results.

Spectroscopic, molecular docking and molecular dynamic simulation studies on the complexes of ß-lactoglobulin, safranal and oleuropein.

Herbal bioactive compounds have captured pronounced attention considering their health-promoting effects as well as their functional properties. In this study, the binding mechanism between milk protein bovine ß-lactoglobulin (ß-LG), oleuropein (OLE) and safranal (SAF) found in olive leaf extract and saffron, respectively via spectroscopic and in silico studies. Fluorescence quenching information exhibited that interactions with both ligands were spontaneous and hydrophobic interactions were dominant. Also, the CD spectroscopy results demonstrated the increase in ß-sheet structure and decrease in the α-helix content for both ligands. Size of ß-LG-OLE complex was higher than ß-LG-SAF due to the conformation and larger molecular size. Molecular docking and simulation studies revealed that SAF and OLE bind in the central calyx of ß-LG and the surface of ß-LG next to hydrophobic residues. Lastly, OLE formed a more stabilized complex compared to SAF based on the molecular dynamic simulation results.

Electrochemical generation of microbubbles by carbon nanotube interdigital electrodes to increase the permeability and material uptakes of cancer cells.

Artificial cavitation as a prerequisite of sonoporation, plays an important role on the ultrasound (US) assisted drug delivery systems. In this study, we have proposed a new method of microbubble (MB) generation by local electrolysis of the medium. An integrated interdigital array of three-electrode system was designed and patterned on a nickel-coated quartz substrate and then, a short DC electrical pulse was applied that consequently resulted in distributed generation of microbubbles at the periphery of the electrodes. Growth of the carbon nanotube (CNT) nanostructures on the surface of the electrodes approximately increased the number of generated microbubbles up to 7-fold and decreased their average size from ∼20 µm for bare to ∼7 µm for CNT electrodes. After optimizing the three-electrode system, biocompatibility assays of the CNT electrodes stimulated by DC electrical micropulses were conducted. Finally, the effect of the proposed method on the sonoporation efficiency and drug uptake of breast cells were assessed using cell cycle and Annexin V/PI flow cytometry analysis. These results show the potential of electrochemical generation of MBs by CNT electrodes as an easy, available and promising technique for artificial cavitation and ultrasound assisted drug delivery.

Microneedle-Based Generation of Microbubbles in Cancer Tumors to Improve Ultrasound-Assisted Drug Delivery.

Production of local microbubbles (MBs) with dense distribution in tumor environment is achieved by developing an integrated electrochemical stimulator on a microfabricated silicon needle covered by zinc-oxide nanowires (ZnONWs). MBs are then exploded by external ultrasonic actuation, which induce microcavitations in tumor cells followed by direct entrance of anticancer drugs into cancer cells. This system, named ZnO nanowire-based microbubble generator probe (ZnONW-MGP), is tested on tumorized mice models (by MC4L2 breast cell lines). Mice treated by ZnONW-MGP have ≈82% reduction in tumor size within 10 days with just 25% of conventional dose of paclitaxel while in the absence of the system, they have just a 15% reduction in tumor size. Presence of ZnO nanostructures on microneedles strongly reduces the size of MBs and enhances the efficacy of the sonoporation.