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Full-Text Articles in Medicine and Health Sciences

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde Jun 2021

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …


Potential Molecular Mechanisms Of Rare Anti-Tumor Immune Response By Sars-Cov-2 In Isolated Cases Of Lymphomas, Debmalya Barh, Sandeep Tiwary, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky Jan 2021

Potential Molecular Mechanisms Of Rare Anti-Tumor Immune Response By Sars-Cov-2 In Isolated Cases Of Lymphomas, Debmalya Barh, Sandeep Tiwary, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex …


The Participation Of The Intrinsically Disordered Regions Of The Bhlh-Pas Transcription Factors In Disease Development, Marta Kolonko-Adamska, Vladimir N. Uversky, Beata Greb-Markiewicz Jan 2021

The Participation Of The Intrinsically Disordered Regions Of The Bhlh-Pas Transcription Factors In Disease Development, Marta Kolonko-Adamska, Vladimir N. Uversky, Beata Greb-Markiewicz

Molecular Medicine Faculty Publications

The basic helix–loop–helix/Per-ARNT-SIM (bHLH-PAS) proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, ranging from differentiation and development control by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for regulation of their activity. Our aim was to analyze the potential connection between disordered regions of the bHLH-PAS transcription factors, post-transcriptional modifications and liquid-liquid phase separation, in the context of disease-associated missense mutations. Highly flexible disordered regions, enriched in short motives which …