Publications by authors named "Michaela M Hatch"

Background: Autologous fat grafting is commonly used for soft-tissue repair (approximately 90,000 cases per year in the United States), but outcomes are limited by volume loss (20% to 80%) over time. Human allograft adipose matrix (AAM) stimulates de novo adipogenesis in vivo, but retention requires optimization. The extracellular matrix derived from superficial fascia, interstitial within the adipose layer, is typically removed during AAM processing.

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Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening and disease modeling tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system (tumor-on-a-chip) that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor-stromal interactions.

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  • Extracellular matrix (ECM) is crucial for tissue function as it influences cell behavior through mechanical and biochemical signals, and changes in ECM can lead to cancer progression.
  • The study compared ECM extracted from normal human colon tissue and metastatic colon tumors, revealing differences in protein composition and stiffness, which affected vascular network formation and tumor growth.
  • By analyzing NADH levels in tumor and endothelial cells, the research showed that tumor ECM increases glycolytic activity in cancer cells, highlighting the ECM's significant role in cancer cell growth and vasculature development.
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  • The study explores the effectiveness of immunotherapy targeting phosphatidylserine in tumors and its combination with anti-PD-1 antibody therapy in breast cancer models, including triple-negative types.
  • Experiments on mice with breast tumors showed that the combination treatment not only inhibited tumor growth more effectively but also improved survival rates compared to either treatment alone.
  • Results indicated that this combined therapy enhanced immune responses, marked by increased tumor-infiltrating lymphocytes and improved resistance to further tumor challenges, alongside significant changes in immune profile assessments.
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  • CXCL12 promotes angiogenesis by activating the mTORC2 signaling pathway in endothelial cells, as opposed to mTORC1.
  • Disruption experiments indicate that mTORC2 is essential for microvascular sprouting, while mTORC1 is not involved.
  • Inhibition of mTORC2 in a mouse model leads to a significant reduction in both tumor angiogenesis and tumor size, linking it to metabolic regulation through the enzyme PFKFB3.
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  • Phosphatidylserine (PS) suppresses immune responses in tumor-bearing animals, potentially undermining the effectiveness of immune checkpoint therapies.
  • Administering PS-targeting antibodies alongside immune checkpoint inhibitors (CTLA-4 or PD-1) in melanoma-bearing mice significantly improves tumor growth inhibition compared to using either treatment alone.
  • The combination therapy also boosts the presence of tumor-infiltrating lymphocytes and enhances proinflammatory cytokine production, indicating a strengthened immune response against tumors.
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