Publications by authors named "Stephanie L Ham"

Background: Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce formation of faecal fatty acid soaps and to improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants' gut microbiota composition and to confirm the beneficial effects of the formula on formation of faecal fatty acid soaps and stool consistency.

Methods: Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial.

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Tumor stroma is a major contributor to the biological aggressiveness of cancer cells. Cancer cells induce activation of normal fibroblasts to carcinoma-associated fibroblasts (CAFs), which promote survival, proliferation, metastasis, and drug resistance of cancer cells. A better understanding of these interactions could lead to new, targeted therapies for cancers with limited treatment options, such as triple negative breast cancer (TNBC).

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Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins.

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Spheroids present a biologically relevant model of avascular tumors and a unique tool for discovery of anti-cancer drugs. Despite being used in research laboratories for several decades, spheroids are not routinely used for drug discovery primarily due to the difficulty of mass-producing uniformly-sized spheroids and intense labor involved in handling, drug treatment, and analyzing them. We overcome this barrier using a novel technology to robotically microprint spheroids in standard 384-well plates.

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Spheroids present a biologically relevant three-dimensional model of avascular tumors and a unique tool for discovery of anticancer drugs. Despite being used in research laboratories for several decades, spheroids are not routinely used in the mainstream drug discovery pipeline primarily due to the difficulty of mass-producing uniformly sized spheroids and intense labor involved in handling, drug treatment, and analyzing spheroids. We overcome this barrier using a polymeric aqueous two-phase microtechnology to robotically microprint spheroids of well-defined size in standard 384-microwell plates.

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Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities.

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Tumors are three-dimensional tissues where close contacts between cancer cells, intercellular interactions between cancer and stromal cells, adhesion of cancer cells to the extracellular matrix, and signaling of soluble factors modulate functions of cancer cells and their response to therapeutics. Three-dimensional cultures of cancer cells overcome limitations of traditionally used monolayer cultures and recreate essential characteristics of tumors such as spatial gradients of oxygen, growth factors, and metabolites and presence of necrotic, hypoxic, quiescent, and proliferative cells. As such, three-dimensional tumor models provide a valuable tool for cancer research and oncology drug discovery.

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A major impediment to anti-cancer drug development is the lack of a reliable and inexpensive tumor model to test the efficacy of candidate compounds. This need has emerged due to the insufficiency of widely-used monolayer cultures to predict drug efficacy in vivo. Spheroids, 3D compact clusters of cancer cells, mimic important characteristics of tumors and provide a tissue analog for drug testing.

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Cell migration is a major process that drives metastatic progression of cancers, the major cause of cancer death. Existing chemotherapeutic drugs have limited efficacy to prevent and/or treat metastasis, emphasizing the need for new treatments. We focus on triple negative breast cancer (TNBC), the subtype of breast cancer with worst prognosis and no standard chemotherapy protocols.

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Cancer cell spheroids present a relevant in vitro model of avascular tumors for anti-cancer drug testing applications. A detailed protocol for producing both mono-culture and co-culture spheroids in a high throughput 96-well plate format is described in this work. This approach utilizes an aqueous two-phase system to confine cells into a drop of the denser aqueous phase immersed within the second aqueous phase.

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