Electromechanical Characterization of Human Brain Tissues: A Potential Biomarker for Tumor Delineation.

OBJECTIVE: Accurate identification of surgical margins in brain tumors is of significant prognostic importance. Despite the availability of methods such as 5-ALA and image guidance, recognizing tumor boundary is highly subjective, dependant on recognizing subtle changes in tissue characteristics including texture and color to aid distinction. METHOD: Design and development of a semi-automated system integrated with MEMS-based electromechanical sensors to enable an objective and reliable method of distinguishing tumors from normal brain tissue. Simultaneous electrical impedance and viscoelastic characterization of three types of freshly excised gliomas (glioblastoma (GBM), astrocytoma (AST), and oligodendroglioma (OLI)) (N = 8 each) and seventeen different normal brain regions (N = 6 each) obtained postmortem. RESULTS: The electrical impedance of gliomas (462±56Ω) was found to be significantly lower than corresponding normal (1267±515Ω) regions at 100kHz (p = 7.46e-11). The difference in the impedance between individual tumor types and corresponding normal regions was also statistically significant (p = 1e-8), suggesting accurate tumor delineation. There were distinct differences in the viscoelastic relaxation responses of high-grade and low-grade gliomas. White matter regions demonstrated higher impedance and faster stress relaxation compared to grey matter regions as a characteristic of their structural composition. CONCLUSION: We demonstrate that simultaneous electromechanical characterization of brain tumors and normal brain tissues can be an effective biomarker for tumor delineation, grading, and studying heterogeneity between the brain regions. SIGNIFICANCE: The observations suggest the potential use of the technology in a clinical setting to achieve gross total resection and improve treatment outcomes by helping surgeons perform real-time risk evaluation during surgery.

Extract of Penicillium sclerotiorum an endophytic fungus isolated from Cassia fistula L. induces cell cycle arrest leading to apoptosis through mitochondrial membrane depolarization in human cervical cancer cells.

Seventeen endophytic fungi were isolated from various tissues of Cassia fistula and the ethyl acetate extracts obtained from 21-day cultures of all the endophytic fungal isolates were initially screened for their cytotoxicity against HeLa (human cervical carcinoma) cells using MTT assay. Of these, Penicillium sclerotiorum extract (PSE), significantly affected the viability of HeLa cells in a dose-dependent manner. The extract of P. Sclerotiorum was further analyzed by GC-MS, which showed three compounds, hexadecanoic acid, oleic acid and benzoic acid to be the major active principles in the extracts.The extract was further tested for invitro cytotoxicity against five cancer cell lines. Of the cell lines tested, HeLa cells showed maximum sensitivity followed by A549, while A431 and U251 were moderately sensitive and MCF-7 was insensitive to the treatment. In addition, normal human embryonic kidney cells, HEK293 remained insensitive to the treatment. Furthermore, the mechanism of cytotoxic activity exhibited by PSE was investigated by evaluating cell cycle progression and apoptotic induction in HeLa cells. Cell cycle analysis revealed that the PSE arrested cells at S and G2/M phase of the cell cycle in a dose-dependent manner. Annexin V- Propidium iodide double staining showed that, the extract potentiates apoptosis rather than necrosis in cells. This was supported by the down regulation in the proapoptotic protein BCL2 and up regulation of BAX (BCL2 Associated X), tumor suppressor protein, p53 and Apaf-1 [Apoptotic Peptidase Activating Factor 1]. Loss of mitochondrial membrane potential and a distinct DNA fragmentation pattern observed following the treatment, suggest that the PSE treatment leads to activation of mitochondrial pathway of apoptosis. Further, the extract also exhibited both antioxidant and anti-angiogenic properties. These results indicate that endophytic fungi isolated from medicinal plants may serve as potential sources of the anti-cancerous compounds.