RESUMO
Cancer treatment often involves excisional surgery, but this approach may leave behind minimal residual disease, leading to tumor regrowth. Proinflammatory cytokines and their role in altering residual cancerous cells postsurgery have garnered attention. The study examines how mild intraoperative cooling affects cancer cells and their gene expression. It aims to discover strategies for reducing tumor growth after surgery. Nine cases of solid tumor were included in the study, nine samples were cooled with the Peltier-Seebeck device down to12°C, and cooled and noncooled regions of tumors were analyzed using reverse transcription-polymerase chain reaction. Key transcriptomes, including neural-cadherin, cadherins (CDH), 70-kDa Heat Shock Protein (HSP70), hypoxia-inducible factor (HIF), Y-Box-binding protein 1 (YB-1), matrix metalloproteinase 9 (MMP9), and matrix metalloproteinase 2 (MMP2), were measured to assess the impact of mild hypothermia on cancer cell metabolism and cold shock responses. Analysis of cooled and noncooled regions revealed reduced MMP2/9 levels in cooled regions in five out of seven cases, indicating potential suppression of tumor invasion and metastasis. CDH-1 expression was detected in five cases, with decreased levels observed in cooled regions in most cases, suggesting a role in tumor aggressiveness. YB-1 expression was increased in six out of eight samples, possibly correlating with local recurrence and reduced overall survival times. N-Cad expression was increased in all five samples where it was detected, indicating its potential involvement in tumor cell motility and invasion. HSPs showed a mild increase in four out of five cases following cooling, potentially contributing to tumor cell resistance to cooling-induced apoptosis. Intraoperative mild cooling resulted in the downregulation of key proteins playing a role in invasion and metastasis. However, Elevated YB-1 and N-Cad expression limits cooling's universal application. Further research is necessary to comprehend cooling-related transcriptome changes and their impact on patient outcomes.
RESUMO
There is a critical need for re-evaluation of electrochemical therapy (EChT) approaches of solid tumors to address the challenges of the currently used method: incomplete pathological response. The coexistence of anode and cathode in the tumor region resulted in acid-alkaline mixation (buffered pH) when the electrodes are so near each other (d < 1 cm), and in the non-affected lesions when the electrodes are far from each other (d > 1 cm), both have resulted in intact tumoral lesions in EChT field. Here, we presented a designation model study of EChT with an external anode out of the tumor and filled the tumor with dense distribution of cathode electrodes to completely destroy the tumoral lesions without any remaining vital tumoral residues. Anode was located in a biological ionic gel chamber (located on top of the skin) which mediates the ionic interface between the external anode and intratumoral cathode. Our newly reported method can solve the lack of a comprehensive therapeutic guideline for any solid tumors. A remarkable increase in the efficiency of EChT without any over-treating was achieved by alkaline therapy of the tumor (without any limitation in locating cathodic needles all over the tumor) and an external acidic region on top of the skin in a cylindrical gel chamber. We found that the destructive volumes and treating ability of mice tumors by this newly represented method were more significant than the conventional EChT method in fewer therapy sessions and no damage to the skin (both anode and cathode electrodes inside the tumor) (P < 0.05). Results of this study applied to mouse model tumors shed new light on returning attraction to EChT as a valuable complementary method for treating different types of solid breast tumors.
