The presence of cancer-associated fibroblast in breast cavity side margins is in correlation with the expression of oncoproteins by adjacent epithelial cells: a new era in cancerous potential.

PURPOSE: Cancer-associated fibroblasts (CAFs) are one of the most critical cells in the tumor environment, with crucial roles in cancer progression and metastasis. Due to Field-Effect phenomena (also called field cancerization), the adjacent cavity side area of the margin is histologically normal, but it has been entered into neoplastic transformation due to MCT4 and MCT1 pathways activated by H2O2/ROS oxidative stress agents secreted by CAF in adjacent tumor bed microenvironment. This paper specifically focused on the role of cancer-associated fibroblast in breast tumor beds and its correlation with the presence of scattered cancer cells or onco-protein-activated cells (may be high risk but not completely transformed cancer cells) in the cavity side margins. METHODS: In this study, the glycolytic behavior of non-tumoral cavity side margins was examined using carbon nanotube-based electrochemical biosensors integrated into a cancer diagnostic probe. This method enabled the detection of CAF accumulation sites in non-cancerous neighboring tissues of tumors, with a correlation to CAF concentration. Subsequently, RT-PCR, fluorescent, histopathological, and invasion assays were conducted on hyperglycolytic lesions to explore any correlation between the abundance of CAFs and the electrochemical responses of the non-cancerous tissues surrounding the tumor, as well as their neoplastic potential. RESULTS: We observed overexpression of cancer-associated transcriptomes as well as the presence and hyperactivation of CAFs in cavity-side regions in which glycolytic metabolism was recorded, independent of the histopathological state of the lesion. At mean 70.4%, 66.7%, 70.4%, and 44.5% increments were observed in GLUT-1, MMP-2, N-cadherin, and MMP-9 transcriptomes by highly glycolytic but histologically cancer-free expression samples in comparison with negative controls (histologically non-cancer lesions with low glycolytic behavior). CONCLUSION: The presence of CAFs is correlated with the presence of high glycolytic metabolism in the cavity margin lesion, high ROS level in the lesion, and finally aggressive cancer-associated proteins (such as MMP2, …) in the margin while these metabolomes, molecules, and proteins are absent in the margins with negatively scored CDP response and low ROS level. So, it seems that when we observe CAFs in glycolytic lesions with high ROS levels, some high-risk epithelial breast cells may exist while no histological trace of cancer cells was observed. Further research on CAFs could provide valuable insights into the local recurrence of malignant breast diseases. Hence, real-time sensors can be used to detect and investigate CAFs in the non-tumoral regions surrounding tumors in cancer patients, potentially aiding in the prevention of cancer recurrence.

Hydroelectric actuator for 3-dimensional analysis of electrophoretic and dielectrophoretic behavior of cancer cells; suitable in diagnosis and invasion studies.

Cancer is a cellular-based disease, so cytological diagnosis is one of the main challenges for its early detection. An extensive number of diagnostic methods have been developed to separate cancerous cells from normal ones, in electrical methods attract progressive attention. Identifying and specifying different cells requires understanding their dielectric and electric properties. This study evaluated MDA-MB-231, HUVEC, and MCF-10A cell lines, WBCs isolated from blood, and patient-derived cell samples with a cylindrical body with two transparent FTO (fluorine-doped tin oxide) plate electrodes. Cell mobility rates were recorded in response to these stimuli. It was observed that cancer cells demonstrate drastic changes in their motility in the presence and absence of an electric field (DC/AC). Also, solution viscosity's effect on cancer cells' capturing efficacy was evaluated. This research's main distinguished specification uses a non-microfluidic platform to detect and pathologically evaluate cytological samples with a simple, cheap, and repeatable platform. The capturing procedure was carried out on a cytological slide without any complicated electrode patterning with the ability of cytological staining. Moreover, this platform successfully designed and experimented with the invasion assay (the ability of captured cancer cells to invade normal cells).

Electrochemical measuring of reactive oxygen species levels in the blood to detect ratio of high-density neutrophils, suitable to alarm presence of cancer in suspicious cases.

Here for the first time, a real-time electrochemical assay on unprocessed blood was designed to detect the presence of cancer in patients. The system has been based on the recently approved pathway, which indicates that the abundance of immature and mature low-density neutrophils (LDNs) with reduced ROS production in peripheral blood is increased with the presence of active cancer tumors. Reduced ROS/H2O2 released from LDNs play the main role in determining the ROS/H2O2 levels of peripheral blood. In contrast, HDNs with increased levels of released ROS/H2O2 have higher concentrations than LDNs in normal cases. Hence, the reduced level of ROS species in peripheral blood recorded by our carbon nanostructure decorated sensor in less than 30 seconds showed a great pre-warning about the presence of non-treated cancer in patients with suspicious mass who have been sent for further evaluations.