Cracking the code: predicting tumor microenvironment enabled chemoresistance with machine learning in the human tumoroid models.

High-grade serous tubo-ovarian cancer (HGSC) is marked by substantial inter- and intra-tumor heterogeneity. The tumor microenvironments (TME) of HGSC show pronounced variability in cellular make-up across metastatic sites, which is linked to poorer patient outcomes. The influence of cellular composition on therapy sensitivity, including chemotherapy and targeted treatments, has not been thoroughly investigated.

Co-stimulation with equibiaxial strain and pre-osteoblast co-culture differentiates monocytes in a bone model.

Bone remodeling and immune function are dynamically regulated through cell-cell and cell-matrix interactions by stem and mature cell populations. We investigated the hypothesis that monocytes and pre-osteoblasts respond to cyclic tensile stress and paracrine interactions by differentiating into macrophage-like and osteoblast-like cells. 20% cyclic equibiaxial strain was applied to monocytic U937 and pre-osteoblastic ST2 cells for 72 h.

Tumoroid model recreates clinically relevant phenotypes of high grade serous ovarian cancer (HGSC) cells, carcinoma associated fibroblasts, and macrophages.

Ovarian cancer, the gynecological malignancy with the lowest survival rate, is significantly influenced by the tumor microenvironment. The mesenchymal subtype of high-grade serous carcinoma (HGSC) shows poor outcomes due to high stromal and low immune response. Single-cell RNA sequencing (scRNA-seq) of HGSC metastatic ascites has identified carcinoma-associated fibroblasts (CAFs), macrophages, and carcinoma-associated mesenchymal stem cells (CA-MSCs) as crucial drivers of immune exclusion, chemotherapy resistance, metastasis, and stem-like cell propagation.

Cracking the Code: Predicting Tumor Microenvironment Enabled Chemoresistance with Machine Learning in the Human Tumoroid Models.

High-grade serous tubo-ovarian cancer (HGSC) is marked by substantial inter- and intra-tumor heterogeneity. The tumor microenvironments (TME) of HGSC show pronounced variability in cellular make-up across metastatic sites, which is linked to poorer patient outcomes. The influence of cellular composition on therapy sensitivity, including chemotherapy and targeted treatments, has not been thoroughly investigated.

Ascitic Shear Stress Activates GPCRs and Downregulates Mucin 15 to Promote OvarianCancer Malignancy.

The accumulation of ascites in patients with ovarian cancer increases their risk of transcoelomic metastasis. Although common routes of peritoneal dissemination are known to follow distinct paths of circulating ascites, the mechanisms that initiate these currents and subsequent fluid shear stresses are not well understood. Here, we developed a patient-based, boundary-driven computational fluid dynamics model to predict an upper range of fluid shear stress generated by the accumulation of ascites.

ANTIMICROBIAL WOUND DRESSINGS FOR FULL-THICKNESS INFECTED BURN WOUNDS.

Infection of wounds delays healing, increases treatment costs, and leads to major complications. Current methods to manage such infections include antibiotic ointments and antimicrobial wound dressings, both of which have significant drawbacks, including frequent reapplication and contribution to antimicrobial resistance. In this work, we developed wound dressings fabricated with a medical-grade polyurethane coating composed of natural plant secondary metabolites, cinnamaldehyde, and alpha-terpineol.

Co-Delivery Polymeric Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles to Target Cancer Stem-Like Cells.

Nanoparticle drug delivery has been promoted as an effective mode of delivering antineoplastic therapeutics. However, most nanoparticle designs fail to consider the multifaceted tumor microenvironment (TME) that produce pro-tumoral niches, which are often resistant to chemo- and targeted therapies. In order to target the chemoresistant cancer stem-like cells (CSCs) and their supportive TME, in this chapter we describe a nanoparticle-based targeted co-delivery that addresses the paracrine interactions between CSC and non-cancerous mesenchymal stem cells (MSCs) in the TME.

Multicellular Tumoroids for Investigating Cancer Stem-Like Cells in the Heterogeneous Tumor Microenvironment.

Cancer stem-like cells (CSC) are a major contributing factor to chemoresistance, tumor recurrence, and poor survival outcomes in patients across cancer types. Signaling from non-tumor cells in the tumor microenvironment (TME) enriches for and supports CSC. This complex cell-cell signaling in the heterogeneous TME presents a challenge for patient survival; however, it also presents an opportunity to develop new targeted therapies that can inhibit survival of CSC.

Applications of Innovation Technologies for Personalized Cancer Medicine: Stem Cells and Gene-Editing Tools.

Personalized medicine is a new approach toward safer and even cheaper treatments with minimal side effects and toxicity. Planning a therapy based on individual properties causes an effective result in a patient's treatment, especially in a complex disease such as cancer. The benefits of personalized medicine include not only early diagnosis with high accuracy but also a more appropriate and effective therapeutic approach based on the unique clinical, genetic, and epigenetic features and biomarker profiles of a specific patient's disease.

Gender bias in reference letters for residency and academic medicine: a systematic review.

Reference letters play an important role for both postgraduate residency applications and medical faculty hiring processes. This study seeks to characterise the ways in which gender bias may manifest in the language of reference letters in academic medicine. In particular, we conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Surfaces with instant and persistent antimicrobial efficacy against bacteria and SARS-CoV-2.

Surfaces contaminated with bacteria and viruses contribute to the transmission of infectious diseases and pose a significant threat to global public health. Modern day disinfection either relies on fast-acting (>3-log reduction within a few minutes), yet impermanent, liquid-, vapor-, or radiation-based disinfection techniques, or long-lasting, but slower-acting, passive antimicrobial surfaces based on heavy metal surfaces, or metallic nanoparticles. There is currently no surface that provides instant and persistent antimicrobial efficacy against a broad spectrum of bacteria and viruses.

Atovaquone: An Inhibitor of Oxidative Phosphorylation as Studied in Gynecologic Cancers.

Oxidative phosphorylation is an active metabolic pathway in cancer. Atovaquone is an oral medication that inhibits oxidative phosphorylation and is FDA-approved for the treatment of malaria. We investigated its potential anti-cancer properties by measuring cell proliferation in 2D culture.

Injectable three-dimensional tumor microenvironments to study mechanobiology in ovarian cancer.

Epithelial ovarian cancers are among the most aggressive forms of gynecological malignancies. Despite the advent of poly adenosine diphosphate-ribose polymerase (PARP) and checkpoint inhibitors, improvement to patient survival has been modest. Limited in part by clinical translation, beneficial therapeutic strategies remain elusive in ovarian cancers.

A Bioreactor for 3D Modeling of the Mechanical Stimulation of Osteocytes.

The bone is a mechanosensitive organ that is also a common metastatic site for prostate cancer. However, the mechanism by which the tumor interacts with the bone microenvironment to further promote disease progression remains to be fully understood. This is largely due to a lack of physiological yet user-friendly models that limit our ability to perform in-depth mechanistic studies.

The Role of the Tumor Microenvironment in CSC Enrichment and Chemoresistance: 3D Co-culture Methods.

Cancer stem-like cells (CSC) are responsible for tumor progression, chemoresistance, recurrence, and poor outcomes in many cancers, making them critical research and therapeutic targets. One of the critical components potentiating CSC chemoresistance is the interactions between CSC and the surrounding cells in the tumor microenvironment. Our lab has developed several 3D co-culture models to study ovarian CSC interactions with stromal or immune cells found in ovarian tumor microenvironments.

Design and applications of surfaces that control the accretion of matter.

Surfaces that provide control over liquid, solid, or vapor accretion provide an evolutionary advantage to numerous plants, insects, and animals. Synthetic surfaces inspired by these natural surfaces can have a substantial impact on diverse commercial applications. Engineered liquid and solid repellent surfaces are often designed to impart control over a single state of matter, phase, or fouling length scale.

Novel Omniphobic Platform for Multicellular Spheroid Generation, Drug Screening, and On-Plate Analysis.

Multicellular spheroids are superior to other culture geometries in reproducing critical physiological conditions of tumors, such as the diffusion of oxygen, nutrients, waste, and drugs, leading to a more precise model of drug sensitivity and resistance. Previously reported spheroid culture platforms are often difficult to use, expensive, single-use, or mechanically unstable. Here, we report a facile, mechanically stable, high-throughput spheroid culture platform based on hierarchically textured omniphobic surfaces.

Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model.

Intractable human diseases such as cancers, are context dependent, unique to both the individual patient and to the specific tumor microenvironment. However, conventional cancer treatments are often nonspecific, targeting global similarities rather than unique drivers. This limits treatment efficacy across heterogeneous patient populations and even at different tumor locations within the same patient.

The MEK1/2 Pathway as a Therapeutic Target in High-Grade Serous Ovarian Carcinoma.

High-grade serous ovarian carcinoma (HGSOC) is the deadliest of gynecological cancers due to its high recurrence rate and acquired chemoresistance. RAS/MEK/ERK pathway activation is linked to cell proliferation and therapeutic resistance, but the role of MEK1/2-ERK1/2 pathway in HGSOC is poorly investigated. We evaluated MEK1/2 pathway activity in clinical HGSOC samples and ovarian cancer cell lines using immunohistochemistry, immunoblotting, and RT-qPCR.

Lysis and direct detection of coliforms on printed paper-based microfluidic devices.

Coliforms are one of the most common families of bacteria responsible for water contamination. Certain coliform strains can be extremely toxic, and even fatal if consumed. Current technologies for coliform detection are expensive, require multiple complicated steps, and can take up to 24 hours to produce accurate results.

Carcinoma-Associated Mesenchymal Stem Cells Promote Chemoresistance in Ovarian Cancer Stem Cells via PDGF Signaling.

Within the ovarian cancer tumor microenvironment, cancer stem-like cells (CSC) interact with carcinoma associated mesenchymal stem/stromal cells (CA-MSC) through multiple secreted cytokines and growth factors. These paracrine interactions have been revealed to cause enrichment of CSC and their chemoprotection; however, it is still not known if platelet-derived growth factor (PDGF) signaling is involved in facilitating these responses. In order to probe this undiscovered bidirectional communication, we created a model of ovarian malignant ascites in the three-dimensional (3D) hanging drop heterospheroid array, with CSC and CA-MSC.

Compressive Stimulation Enhances Ovarian Cancer Proliferation, Invasion, Chemoresistance, and Mechanotransduction via CDC42 in a 3D Bioreactor.

This report investigates the role of compressive stress on ovarian cancer in a 3D custom built bioreactor. Cells within the ovarian tumor microenvironment experience a range of compressive stimuli that contribute to mechanotransduction. As the ovarian tumor expands, cells are exposed to chronic load from hydrostatic pressure, displacement of surrounding cells, and growth induced stress.

Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.

BACKGROUNDEpidemiologic studies suggest that metformin has antitumor effects. Laboratory studies indicate metformin impacts cancer stem-like cells (CSCs). As part of a phase II trial, we evaluated the impact of metformin on CSC number and on carcinoma-associated mesenchymal stem cells (CA-MSCs) and clinical outcomes in nondiabetic patients with advanced-stage epithelial ovarian cancer (EOC).

Expansion of Circulating Tumor Cells from Patients with Locally Advanced Pancreatic Cancer Enable Patient Derived Xenografts and Functional Studies for Personalized Medicine.

Improvement in pancreatic cancer treatment represents an urgent medical goal that has been hampered by the lack of predictive biomarkers. Circulating Tumor Cells (CTCs) may be able to overcome this issue by allowing the monitoring of therapeutic response and tumor aggressiveness through ex vivo expansion. The successful expansion of CTCs is challenging, due to their low numbers in blood and the high abundance of blood cells.