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Articles 1 - 5 of 5

Full-Text Articles in Cell Biology

Hypoxic Influences On Myeloid Cells During Inflammation And Inflammation-Associated Cancer, Nan Lin Jan 2018

Hypoxic Influences On Myeloid Cells During Inflammation And Inflammation-Associated Cancer, Nan Lin

Publicly Accessible Penn Dissertations

Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their progression. Macrophages and neutrophils are major cellular components of innate immunity and contribute not only to O2 deprivation at the site of inflammation, but also alter many of their functions in response to hypoxia to either facilitate or suppress inflammation. Hypoxia stabilizes HIF-αs in macrophages and neutrophils, and these O2-sensitive transcription factors are key regulators of inflammatory responses in myeloid cells. This body of work investigates the role of myeloid HIF-αs in the settings of several acute and chronic inflammatory diseases.

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Targeting Stress Response Pathways In Soft Tissue Sarcoma: The Role Of Hypoxia And Autophagy In Tumor Survival, Michael Nakazawa Jan 2015

Targeting Stress Response Pathways In Soft Tissue Sarcoma: The Role Of Hypoxia And Autophagy In Tumor Survival, Michael Nakazawa

Publicly Accessible Penn Dissertations

Soft tissue sarcomas (STS) are a group of malignancies that arise from mesenchymal tissue, consisting of over 50 distinct histiologic subtypes. Unfortunately, the five-year survival rate of sarcoma patients has remained relatively unchanged, and due to the rarity of the disease, research and development of adequate therapeutics for STS lags behind other cancers. Therefore, understanding the molecular drivers of STS is important in developing new therapeutics, as well as discovering druggable processes that occur across multiple subtypes. One feature common to STS is hypoxia, or low O2 conditions. Using molecular biology, biochemical approaches, genetically engineered mouse models, as well as ...


Proliferation And Survival Mechanisms In Soft Tissue Sarcoma And Glioblastoma Tumors, Vera Mucaj Jan 2014

Proliferation And Survival Mechanisms In Soft Tissue Sarcoma And Glioblastoma Tumors, Vera Mucaj

Publicly Accessible Penn Dissertations

Soft tissue sarcomas and glioblastomas are two deadly tumors that are characterized by aggressive overproliferation, and regions of severe intratumoral nutrient and oxygen deprivation. The mechanisms by which tumors evade proliferation control signals and survive in a hostile microenvironment are active areas of investigation. This work describes two projects investigating loss of proliferation control in soft tissue sarcoma, as a result of Hippo pathway deregulation, and mechanisms of survival under stress in glioblastoma, as a result of decreased microRNA-124 (miR-124) levels. First, we demonstrate that the Hippo pathway is deregulated in soft tissue sarcoma patient samples, leading to overexpression of ...


Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay Jan 2014

Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay

Publicly Accessible Penn Dissertations

Hypoxia-inducible factors (HIFs) mediate adaptation to low O2, or hypoxia, are important at every stage of tumor initiation, and impact the progression of a variety of diseases, including colorectal cancer. This body of work investigates the role of hypoxia and HIF-mediated signaling in both tumor cells and macrophages across the natural history of inflammation-induced cancers. First, the effect of HIF inhibition in tumor parenchyma and stroma in extant colitis-associated colon carcinomas (CAC) is investigated using acriflavine (ACF), a naturally occurring compound known to repress HIF transcriptional activity. Pharmacologic HIF inhibition represents a novel therapeutic strategy for cancer treatment and data ...


Hypoxic Regulation Of Myc And Epidermal Barrier Development, Waihay J. Wong Jan 2012

Hypoxic Regulation Of Myc And Epidermal Barrier Development, Waihay J. Wong

Publicly Accessible Penn Dissertations

Low O2 tension, or hypoxia,activates a complex transcriptional program via hypoxia-inducible factors (HIFs) to facilitate adaptation to low-O2 conditions. This work describes two instances of HIF activity in normal tissue development and disease progression. First, HIF is partly responsible for MYC inhibition in hypoxic human colon carcinoma cells. Hypoxic MYC down-regulation requires the E3 ubiquitin ligases FBXW7 and DDB1, as well as cytosolic cathepsins. Reduced MYC protein correlated with hypoxic inhibition of RNA polymerase III-dependent MYC target genes, suggesting that MYC suppression under hypoxia occurs independently of its binding partner MAX. MYC overexpression in hypoxic cells induced ...