Open Access. Powered by Scholars. Published by Universities.®

Cell Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 4 of 4

Full-Text Articles in Cell Biology

Manipulating The Tumor Microenvironment For Therapeutic Benefit, Kate M. Bailey Jun 2014

Manipulating The Tumor Microenvironment For Therapeutic Benefit, Kate M. Bailey

Graduate Theses and Dissertations

The physical tumor microenvironment contributes significantly to carcinogenesis, cancer progression and metastatic dissemination. Two main components of the tumor microenvironment, hypoxia and acidosis, are present in nearly every solid tumor and act as powerful selection forces against the tumor. Hypoxia and acidosis promote tumor heterogeneity and contribute to chemotherapy and radiotherapy resistance. This dissertation interrogates methods to target the tumor microenvironment including two novel studies describing mechanisms of buffer therapy resistance and targeting tumor hypoxia with vasodilators to enhance the efficacy of a hypoxia activated prodrug, TH-302.

In the first study, mechanisms of buffer therapy resistance were identified and detailed ...


Cellular Coping Mechanisms To Hypoxia In The Longhorn Sculpin (Myoxocephalus Octodecemspinosus) Brain, Kelly Heino Jan 2014

Cellular Coping Mechanisms To Hypoxia In The Longhorn Sculpin (Myoxocephalus Octodecemspinosus) Brain, Kelly Heino

Electronic Theses and Dissertations

The loss of neurological function due to hypoxia remains to be a challenge in many species due to the lack of knowledge and understanding of cellular responses. To investigate cellular responses and survival strategies of the brain during hypoxia and post-hypoxia recovery in a moderate hypoxia-tolerant species, with the hopes of identifying possible therapeutic remedies, thirty Longhorn sculpin, Myoxocephalus octodecimspinosus, were challenged with acute hypoxia (40% O2 saturation for 1 h) and twelve additional sculpin were used as controls (~90% O2 saturation). Fish were sampled at each of the following time points: control/normoxic conditions (T=0 h); hypoxic ...


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 ...