Cancer Biology Commons^™

Perplexing Role Of P-Glycoprotein In Tumor Microenvironment, Kianna Robinson, Venkataswarup Tiriveedhi

Biology Faculty Research

Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regimen following development of MDR achieved limited beneficial outcomes. While, …

Modulation Of The Pol Ii Ctd Phosphorylation Code By Rac1 And Cdc42 Small Gtpases In Cultured Human Cancer Cells And Its Implication For Developing A Synthetic-Lethal Cancer Therapy, Bo Zhang, Xuelin Zhong, Moira Sauane, Yihong Zhao, Zhi-Liang Zheng

Publications and Research

Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD …

Pan-Cancer Analysis Reveals Cooperativity Of Both Strands Of Microrna That Regulate Tumorigenesis And Patient Survival, Ramkrishna Mitra, Clare M. Adams, Wei Jiang, Evan J. Greenawalt, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Recently, both 5p and 3p miRNA strands are being recognized as functional instead of only one, leaving many miRNA strands uninvestigated. To determine whether both miRNA strands, which have different mRNA-targeting sequences, cooperate to regulate pathways/functions across cancer types, we evaluate genomic, epigenetic, and molecular profiles of >5200 patient samples from 14 different cancers, and RNA interference and CRISPR screens in 290 cancer cell lines. We identify concordantly dysregulated miRNA 5p/3p pairs that coordinately modulate oncogenic pathways and/or cell survival/growth across cancers. Down-regulation of both strands of miR-30a and miR-145 recurrently increased cell cycle pathway genes and significantly reduced patient …

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …

Molecular Mechanisms Underlying Migratory And Immune-Evasion Properties Of Circulating Tumor Cells, Jeannette A. Huaman

Dissertations, Theses, and Capstone Projects

Metastasis is the leading cause of cancer deaths worldwide. However, there exist only limited treatment options and they are often ineffective. An important aspect of metastasis that requires study, but has previously been understudied is circulating tumor cells (CTCs). CTCs are a critical step in the metastatic cascade. They can be analyzed for the identification of key mechanisms in metastasis. To this end, we isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these mouse models, primary tumor and CTC lines were established. Functional characterization of …

10th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The Annual Postdoctoral Science Symposium (APSS) was initiated on August 4, 2011, by the MD Anderson Postdoctoral Association to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience.

APSS is a scientific symposium organized by postdoctoral fellows from The University of Texas MD Anderson Cancer Center that welcomes submissions and presentations from postdoctoral fellows from all Texas Medical Center affiliated institutions and other Houston area institutions. The APSS provides a professional venue for postdoctoral scientists to develop, clarify and refine their research as result of formal reviews and critiques …

Breast Cancer Screening Implications Of Risk Modeling Among Female Relatives Of Atm And Chek2 Carriers, Anne E. Weidner, Mariel E. Liggin, Brenda I. Zuniga, Ann L. Tezak, Georgia L. Wiesner, Tuya Pal

Biology Student Research

Background

With the increasing use of multigene panel tests, pathogenic and likely pathogenic (P/LP) variants are identified more frequently in the moderate-penetrance breast cancer genes ATM and CHEK2. Lifetime breast cancer risk among women with P/LP variants in these genes generally exceeds 20%, meeting the threshold at which high-risk breast cancer screening through breast magnetic resonance imaging (MRI) is recommended.

Methods

Among a registry-based sample of 56 ATM and 69 CHEK2 carriers, the authors sought to determine the percentage of relatives in whom a P/LP variant would impact breast cancer surveillance. Lifetime breast cancer risks for unaffected, female first-degree …

Microrna And Transcription Factor Co-Regulatory Networks And Subtype Classification Of Seminoma And Non-Seminoma In Testicular Germ Cell Tumors, Guimin Qin, Saurav Mallik, Ramkrishna Mitra, Aimin Li, Peilin Jia, Christine M. Eischen, Zhongming Zhao

Department of Cancer Biology Faculty Papers

Recent studies have revealed that feed-forward loops (FFLs) as regulatory motifs have synergistic roles in cellular systems and their disruption may cause diseases including cancer. FFLs may include two regulators such as transcription factors (TFs) and microRNAs (miRNAs). In this study, we extensively investigated TF and miRNA regulation pairs, their FFLs, and TF-miRNA mediated regulatory networks in two major types of testicular germ cell tumors (TGCT): seminoma (SE) and non-seminoma (NSE). Specifically, we identified differentially expressed mRNA genes and miRNAs in 103 tumors using the transcriptomic data from The Cancer Genome Atlas. Next, we determined significantly correlated TF-gene/miRNA and miRNA-gene/TF …

Antiproliferative And Apoptotic Effects Of Proteins From Black Seeds (Nigella Sativa) On Human Breast Mcf-7 Cancer Cell Line, Yamna Khursid, Basir Syed, Shabana U. Simjee, Obaid Beg, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line.

Methods

NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration …

Novel Roles Of Tobacco-Associated Genes Underlying Disparate Survival In Appalachian Head And Neck Squamous Cell Carcinoma, Brenen William Papenberg

Graduate Theses, Dissertations, and Problem Reports

Head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplasm primarily caused by tobacco consumption or human papillomavirus (HPV) infection. Incidence and mortality rates for HNSCC vary geographically. Appalachian residents consume tobacco products to a greater extent than national averages, a risk factor known to promote HPV-negative HNSCC through increased genomic instability. Male Appalachian patients display significantly worse relative survival than Appalachian females or non-Appalachian residents of either sex. Secondary analysis of available cancer registry outcome data from 2007-2013 indicates that white males with stage IV oral cavity/pharyngeal (OC/P) HNSCC are responsible for the decreased male survival observed within …

Ototoxicity Of Cisplatin, Pyriplatin, And Phenathriplatin In The Auditory Hybridoma Cell Line, Hei-Oc1, Alexandra Johnston

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anti-cancer drug which is effective against several cancers, but also causes harmful side-effects, including ototoxicity and hearing loss. While cisplatin is a bifunctional compound that forms coordinate covalent bonds with both strands of DNA, recently investigated monofunctional platinum(II) compounds bind to only one DNA strand, and may activate different cell-death mechanisms. As several monofunctional platinum(II) compounds have anti-cancer properties, but could target different cell-death pathways, they could potentially have different and reduced side-effects. In this study, the HEI-OC1 auditory hybridoma cell line was used to investigate the ototoxicity of cisplatin and two monofunctional platinum(II) compounds, phenanthriplatin and …

Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin

Articles

Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50–60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).

Development Of Methodologies For Raman Spectral Analysis Of Human Saliva For Detection Of Oral Cancer, Genecy Calado

Doctoral

Oral cancer is one of the most common malignancies worldwide, with over 350,000 to 400,000 new cases reported each year. Early detection, followed by appropriate treatment, can increase cure rates to 80 or 90%, and greatly improve the quality of life by minimising extensive, debilitating treatments. Usually, the clinical diagnosis of most head and neck neoplasms, including oral cancer, is performed through time-consuming and invasive biopsies followed by histological examination of the excised tissue and may present psychological trauma and risk of infection to patients. In addition, histological grading can be subjective, as it is based on subtle morphological changes. …

Identification Of Imiquimod As A Potential Combination For Anti-Cd47 Antibodies In Cancer Therapy, Nicole Brittaney Pang

Scripps Senior Theses

The avenues of targeted immunotherapy offers a promise of less toxic treatment options for those battling different forms of cancer. Specifically, the process of hijacking a patient’s own immune system to fight cancer from within versus using external treatments like chemotherapy which is extremely damaging to the patient. One such avenue includes the usage of monoclonal antibodies as an effective modality for immunotherapy. Cluster of Differentiation 47 (CD47), also known as the ‘don’t eat me signal’, aids in cell proliferation and evasion of phagocytosis and has been found to be a target for stopping tumorigenesis. Previous research has been successful …

Prostate Cancer Resistance To Cabazitaxel Chemotherapy, Diane Begemann

Theses and Dissertations--Toxicology and Cancer Biology

The plasticity of prostate tumors contributes to the heterogeneity in response and acquisition of therapeutic resistance in advanced prostate cancer. Disruption of the phenotypic landscape via epithelial-mesenchymal transition (EMT) enables prostate tumors to invade and metastasize. Our previous studies demonstrated that cabazitaxel (a 2^nd generation FDA-approved taxane chemotherapy) that is used for treatment of castration-resistant prostate cancer (CRPC), causes reversal of EMT to mesenchymal-epithelial transition (MET). The present study examined the effect of sequencing cabazitaxel chemotherapy mediated MET on prostate tumor re-differentiation and its impact on overcoming resistance in models of advanced prostate cancer.

The presence of DHT (1nM) …

Breast Cancer Associated Muscle Fatigue: Novel Targets To Improve Survival And Quality Of Life, Hannah Elizabeth Wilson

Graduate Theses, Dissertations, and Problem Reports

Women diagnosed with breast cancer (BC) currently represent the largest group of cancer survivors in the United States, accounting for over 20% of those living after a cancer diagnosis. Most BC survivors report an unusual degree of fatigue, which can present prior to diagnosis and continue for many years after treatment cessation. Recent studies show that deficits in muscle function predict shorter survival in cancer, perhaps due to the fact that fatigue is known to reduce a patient’s tolerance to anti-cancer therapies. Therefore, improving muscle function in BC patients has the potential to improve both quality of life and survival …

Evidence Of Y Chromosome Long Non-Coding Rnas Involved In The Radiation Response Of Male Non-Small Cell Lung Cancer Cells, Tayvia Brownmiller

Graduate Theses, Dissertations, and Problem Reports

Non-small cell lung cancer (NSCLC) is the number one cause of cancer related mortality in the United States and worldwide. Advanced and therapeutically resistant lung tumors contribute to the high rate of mortality from NSCLC, therefore there is a need for new methods of diagnosing and treating this disease. Long non-coding RNAs (lncRNAs) have been shown to be a crucial component of human molecular biology, regulating nearly every cellular pathway from chromatin condensation to transcription and translation. Furthermore, many lncRNAs have been classified as oncogenes or tumor suppressors, highlighting the various molecular mechanisms they are involved in regarding the formation …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

The Human Intermediate Prolactin Receptor: A Breast Cancer Proto-Oncogene, Jacqueline M. Grible

Theses and Dissertations

The hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was recently found to be oncogenic when co-expressed with wild-type mPRLr. hPRLrI co-expression with full-length hPRLr (hPRLrL) in MCF10AT cells resulted in robust in vivo and in vitro transformation, while hPRLrI knock-down in MCF7 cells significantly decreased in vitro malignant potential. hPRLrL+I heterodimers displayed greater stability than hPRLrL homodimers, and while being capable of activating Jak2, Ras, and MAPK, they were unable to induce …

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Kyle Kenney, Amanda Bohn, Angela Asirvatham

Student Research Poster Presentations 2020

The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The quantity of cAMP available to Schwann cells can determine if they become a myelinating or proliferating phenotype. The abundance of intracellular cAMP available to the cell is widely regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of cAMP in the cell. This study was undertaken to determine the concentration of rolipram that would …

Grainyhead-Like 2 Sensitizes Cells To Natural Killer Cell Cytotoxicity And Promotes The Interferon Response, Ian Philip Macfawn

Graduate Theses, Dissertations, and Problem Reports

Our research determined that the epithelial master transcription factor Grainyhead-like 2 (GRHL2) promotes sensitivity to Natural Killer (NK) cell-mediated killing, and modulates the interferon I (IFN-I) response of epithelial cells. Immune surveillance by NK cells constitutes a major selective pressure for circulating tumor cells. Epithelial (GRHL2-expressing) cells exhibited significantly higher rates of NK conjugation, a crucial step in direct cell-mediated cytotoxicity. Mechanistically, GRHL2 upregulates expression of intercellular adhesion molecule 1 (ICAM-1), a cell surface molecule critical for NK to target cell synaptogenesis. GRHL2 epigenetically regulates gene expression, and we found that GRHL2 mutant proteins unable to interact with the epigenetic …

Characterising Pd-L1 Expression In Circulating Melanoma And Non-Small Cell Lung Cancer Cells, Isaac Spencer

Theses: Doctorates and Masters

Incidence rates for both melanoma and non-small cell lung cancer (NSCLC) have risen in recent decades. While advanced cases of both diseases have previously demonstrated low survivability, novel therapies such as immune checkpoint inhibitors, have significantly improved the outcome of patients suffering from these cancers. Recent clinical trials have led to the United States Food and Drug Administration (FDA) approving the use of antibodies targeting the PD-1 immune checkpoint for both melanoma and NSCLC. Anti-PD-1 antibodies have been seen to illicit responses in up to 40% of patients, however, particularly for melanoma, there is a lack of biomarkers to select …