The Effects of Metronomic and Maximum-Tolerated Dose Chemotherapy in Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy and mRNA Expression

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored. This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and metabolism in primary colorectal tumors receiving MTD and MET. In Chapter 2, we first developed and validated a miniaturized spectroscopy probe that enabled the longitudinal investigation of changes in perfusion in primary tumors. Our results showed that an increase in oxygenation occurs in MET and MTD-treated tumors. In Chapter 3, we presented generalized additive models as an appropriate methodology to analyze the non-linear trends in longitudinal data that are commonly found in biomedical research. In Chapter 4, we sought to provide molecular context to the observed changes in perfusion from Chapter 2 by quantifying relative changes the expression of genes associated with angiogenesis. We found that despite eliciting a similar response, the molecular mechanisms behind increases in perfusion in MET and MTD-treated tumors are different. Specifically, tumors treated with MET presented higher Hif-1a, Aldoa and Pgk1 expression, indicating increased glycolytic activity. Taken together, this work highlights that the opportunities and challenges of MET to treat CRC can be better understood by using combined modalities that complement the information of changes caused by chemotherapy

Mathematical modeling of mpox: A scoping review

Background: Mpox (monkeypox), a disease historically endemic to Africa, has seen its largest outbreak in 2022 by spreading to many regions of the world and has become a public health threat. Informed policies aimed at controlling and managing the spread of this disease necessitate the use of adequate mathematical modeling strategies. Objective: In this scoping review, we sought to identify the mathematical models that have been used to study mpox transmission in the literature in order to determine what are the model classes most frequently used, their assumptions, and the modelling gaps that need to be addressed in the context of the epidemiological characteristics of the ongoing mpox outbreak. Methods: This study employed the methodology of the PRISMA guidelines for scoping reviews to identify the mathematical models available to study mpox transmission dynamics. Three databases (PubMed, Web of Science and MathSciNet) were systematically searched to identify relevant studies. Results: A total of 5827 papers were screened from the database queries. After the screening, 35 studies that met the inclusion criteria were analyzed, and 19 were finally included in the scoping review. Our results show that compartmental, branching process, Monte Carlo (stochastic), agent-based, and network models have been used to study mpox transmission dynamics between humans as well as between humans and animals. Furthermore, compartmental and branching models have been the most commonly used classes. Conclusions: There is a need to develop modeling strategies for mpox transmission that take into account the conditions of the current outbreak, which has been largely driven by human-to-human transmission in urban settings. In the current scenario, the assumptions and parameters used by most of the studies included in this review (which are largely based on a limited number of studies carried out in Africa in the early 80s) may not be applicable, and therefore, can complicate any public health policies that are derived from their estimates. The current mpox outbreak is also an example of how more research into neglected zoonoses is needed in an era where new and re-emerging diseases have become global public health threats