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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty Jan 2023

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …


Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach Dec 2021

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …


Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant Jan 2021

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …


Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites Apr 2017

Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites

Electronic Thesis and Dissertation Repository

Cellular division is primarily controlled at the G1 to S-phase transition of the cell cycle by the retinoblastoma tumor-suppressor protein (pRB). The ability of pRB to restrict S-phase entry is primarily attributed to the repression of E2F transcription factors required to upregulate cell cycle target genes necessary for cellular division. Interestingly, while pRB is disrupted in the vast majority of human cancers, mutations typically target upstream regulators of pRB leading to inactivation through hyperphosphorylation. The rarity of direct pRB mutations suggests that the regulation of the cell cycle by pRB may involve additional mechanisms outside of E2F repression, as this …