11/20/2023
By Maria Anthi Kouri

The Kennedy College of Sciences, Department of Physics and Applied Physics, invites you to attend a Ph.D. Dissertation defense by Maria Anthi Kouri on "Advanced modalities for molecular precision towards the enhancement of cancer diagnosis and therapy."

Degree: Doctor of Philosophy in Physics/Medical Physics
Defense Date: Tuesday, Nov. 21, 2023
Defense Time: 9 a.m.
Location: Olney 108A and via Zoom (Passcode: 609988)

Committee Members

  • Committee Chair/Advisor:​ Erno Sajo, Professor and Director of Medical Physics, Department of Physics and Applied Physics, Kennedy College of Science, University of Massachusetts Lowell
  • Co-Chair/Advisor: Professor Efstathios P. Efstathopoulos, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Greece
  • Wilfred Ngwa, Adjunct Professor, Department of Physics and Applied Physics, Kennedy College of Science, University of Massachusetts Lowell
  • Dionysios Christodouleas, Associate Professor, Department of Chemistry, Center for Pathogen Research & Training (CPRT), Kennedy College of Science, University of Massachusetts Lowell

Abstract: The current study constitutes a comprehensive exploration of advanced molecular techniques for the enhancement of cancer diagnosis and therapy. It addresses the intricate challenges regarding the precise diagnosis, accurate localization, adequate surgical removal of malignancies and targeted therapy. The content is deeply rooted in the paradigm shift toward personalized medicine, which emphasizes the understanding of the unique molecular intricacies of each patient's malignancy.

One of the primaries focuses of this research involves the utilization of Raman spectroscopy (RS) as an adjuvant diagnostic tool that offers molecular information. RS emerged as a powerful technique, offering real-time, in vivo acquisition and analysis of unique spectral fingerprints, revealing the molecular underpinnings of cancer with high sensitivity, specificity, and accuracy. Its objectivity and ability to provide biochemical information and to accurately differentiate cancerous from normal tissue was meticulously examined across various contexts.

Initially, ex vivo experiments were conducted obtaining micro-Raman spectra of malignant and normal colorectal tissues excised from ten patients who underwent open surgery. The biochemical changes in various Raman bands intensities, the lipid rich spectra in the normal samples and the intensity changes in the collagen and protein Raman bands evidenced the accurate spectroscopic discrimination between cancerous and normal tissue.

Following that, in vivo experiments were performed with a portable Raman probe spectrometer at immunosuppressed laboratory animals (SCID male mice) with developed colorectal xerographs towards localization of colorectal cancer malignancies from normal tissue margins. Principal component analysis (PCA) was performed to accommodate discrimination between malignant and normal tissues and to highlight their biochemical differences through loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectroscopy in vivo. Eventually, accuracy reached 89.9% and precision 91.4% regarding tissue classification.

Additionally, this study focused on cervical cancer radiotherapy through the exploration of AuNPs' induced radiosensitivity. Utilizing ex vivo experiments on cancer/normal cell lines, this research dissected intricate radiobiological interactions. The extended analysis of the radiobiological cell survival curves, the dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed insights about the multi-factorial impact of AUNPs’. The outcomes showcased substantial enhancement of radiation responses in cancer cells following AuNPs treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 hours post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells.

The findings presented underscore the significant potential of personalized medicine, emphasizing the importance of molecular precision in cancer diagnosis and therapy. This research paves the way for tailored and efficient molecular approaches in the fight against cancer. The interdisciplinary nature of this study highlights the importance of integrating advanced molecular modalities and cutting-edge technologies in oncological research and hopefully in clinical practice.