Cancer Biology Commons^™

Non-Photic Mechanisms Of Entrainment In Bmal1 Deficient Conditions, Jamie Tran

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Maintaining our internal circadian (i.e. 24 -hour) clock is imperative to our daily biological and mental well-being. Large epidemiological studies have shown that disruptions of our circadian rhythms can lead to poor mental health, metabolic diseases, and various types of cancer. Various external cues that have become a part of the modern times such as electricity, shift -work, rapid travel across various time zones, easier access to nutritionally unbalanced food items, and various rigid social demands have deleterious effects on our internal clock, and generally reduce robustness of the circadian clock. The two following projects aim to examine two ...

Gaps In Patient Education On Safe Handling And Disposal Of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study, Sun Yang, Priya Patel, Alexandra Corcoran, Eric Dobberpuhl, Samantha Isidro, Dustin Le, Analise Klassen, Jay Rho, David Tran, Richard Beuttler, Neda Noori Nassr, Katherine Gruenberg, Siu-Fun Wong

Pharmacy Faculty Articles and Research

Background

Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods

Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher’s exact test computed using the R Project were used for analyses. Results

Pharmacist group (16/25, 62 ...

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME ...

Combined Curcumin And Luteolin Synergistically Inhibit Colon Cancer Associated With Notch1 And Tgf-Β Signaling Pathways In Cultured Cells And Xenograft Mice, Rukayat Aromokeye, Hongwei Si

Human Sciences Faculty Research

This study aimed to select a combination of curcumin and luteolin, two phytochemicals from food, at lower concentrations with a higher inhibitory effect on colon cancer growth and investigate possible molecular mechanisms of this anti-colon cancer effect. By pairwise combination screening, we identified that the combination of curcumin (CUR) at 15 μM and luteolin (LUT) at 30 μM (C15L30) synergistically suppressed the proliferation of human colon cancer CL-188 cells, but the individual chemicals had a little inhibitory effect at the selected concentrations. This result was also confirmed in other colon cancer DLD-1cells, suggesting that this synergistic inhibitory effect of C15L30 ...

Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don

Doctoral Dissertations

Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the ...

Complex Role Of Microbiome In Pancreatic Tumorigenesis: Potential Therapeutic Implications, Suneetha Amara, Li V. Yang, Venkataswarup Tiriveedhi, Mahvish Muzaffar

Biology Faculty Research

Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality with limited diagnostic and therapeutic options. Although immunotherapy has shown promise in the treatment of several cancers, its role in pancreatic cancer is rather limited. Several studies have focused on determining the role of the tumor microenvironment with cancer-cell-intrinsic events and tumor-infiltrating immune cellular properties. However, in the past decade, there has been emerging research aimed at delineating the role of the host microbiome, including the metabolites from microbes and host responses, on pancreatic tumorigenesis. Importantly, there is emerging evidence suggesting the beneficial role of a gut microbiome transplant ...

Low-Salt Diet Reduces Anti-Ctla4 Mediated Systemic Immune-Related Adverse Events While Retaining Therapeutic Efficacy Against Breast Cancer, Durga Khandekar, Debolanle O. Dahunsi, Isaac V. Manzanera Esteve, Sonya Reid, Jeffrey C. Rathmell, Jens M. Titze, Venkataswarup Tiriveedhi

Biology Faculty Research

Immune checkpoint inhibitor (ICI) therapy has revolutionized the breast cancer treatment landscape. However, ICI-induced systemic inflammatory immune-related adverse events (irAE) remain a major clinical challenge. Previous studies in our laboratory and others have demonstrated that a high-salt (HS) diet induces inflammatory activation of CD4+T cells leading to anti-tumor responses. In our current communication, we analyzed the impact of dietary salt modification on therapeutic and systemic outcomes in breast-tumor-bearing mice following anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody (mAb) based ICI therapy. As HS diet and anti-CTLA4 mAb both exert pro-inflammatory activation of CD4+T cells, we hypothesized that a ...

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 ...

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa ...

Visceral Adipose Tissue Remodeling In Pancreatic Ductal Adenocarcinoma Cachexia: The Role Of Activin A Signaling, Pauline Xu

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer death in the United States and is projected to become the second leading cause by the year 2030. Prognosis for patients with metastatic disease remains dismal, with cachexia as a main contributor to the low survival rate. Emerging reports indicate that PDAC patients display distinct phenotypes of cachexia development, with either adipose tissue loss preceding skeletal muscle wasting or loss of only adipose tissue. While muscle wasting has been the most frequently studied mechanism in cachexia research, changes in adipose tissue are increasingly understood as important components of ...

Identifying A Novel Hsp40/J-Domain Protein Inhibitor That Depletes Mutant P53 To Inhibit Cancer Malignancy, Shigeto Nishikawa

Research Days

Background: Accumulation of oncogenic mutant p53 (mutp53) greatly contributes to cancer progression. DNAJA1, which is a member of heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), plays a crucial role in the stabilization of misfolded forms of mutp53. Knockdown of DNAJA1 results in proteasomal degradation of misfolded mutp53, leading to tumor suppression. Currently, no HSP40/JDPs inhibitors are available in clinics.

Objectives/Goal: The goal of this study is to identify and characterize potential anti-cancer compounds which can induce mutp53 degradation by inhibiting HSP40/JDPs.

Methods/Design: To identify compounds that potentially bind to DNAJA1, we performed ...

Targeting Stress Granule Inhibition As A Novel Vulnerability Of Mutant P53, Elizabeth Thoenen

Research Days

Background: Tumor suppressor p53 (p53) inhibits cancer progression by transactivating genes involved in cell cycle arrest and apoptosis. P53 is mutated in half of all human tumors, which is well correlated with poor patient outcomes. Most of p53 mutations are missense mutations. Missense mutant p53 protein (mutp53) not only loses wild-type p53 (wtp53) transcription factor activity, but also shows oncogenic gain of function that enhances metastasis and drug resistance through protein-protein interactions. However, the exact mechanism by which mutp53 induces drug resistance is poorly described. Moreover, strategies that directly target mutp53 have been challenging.

Objectives/Goal: Our goal is to ...

Mdm2 Enhances Taxane Sensitivity By Inducing Stmn1 Degradation, Hongyi Ren

Research Days

Background: MDM2, a major E3 ubiquitin ligase of p53, is overexpressed in ~30% of human cancers. Evidence showed that overexpressed MDM2 has p53-independent oncogenic functions and is correlated with poor prognosis. Given that MDM2 overexpression is cancer-specific, therapies targeting vulnerabilities imposed by MDM2 overexpression may cause cell death specifically in cancer cells with minimum side effects.

Objectives/Goal: Our goal is to identify drugs that specifically kill MDM2-overexpressing cancer cells in a p53- independent manner.

Methods/Design: We generated p53-knockout (p53KO) and p53/MDM2-double knockout (DKO) SJSA-1 osteosarcoma cells in which MDM2 gene is amplified by using the CRISPR-Cas9 system ...

Investigation Of Microbe And Host Tissue Interactions Contributing To The Pathogenesis Of Colorectal Cancer, Ryan Chapman, Dhundy Bastola

Theses/Capstones/Creative Projects

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The pathogenesis of this disease can fall under broad categories; however, the specific precursory mechanism of CRC pathogenesis is still unknown. Dysregulations of the gut microbiome have been identified in the CRC tissue environment. Additionally, CRC tissue gene expression has been observed to differ from that of healthy tissue. Despite these noticeable changes, few studies have directly compared the microorganism composition to the gene expression of CRC tissue. Doing so may identify whether the differentially abundant microorganisms influence the changes in gene expression. The goal of this ...

Metabolism In The Colonocyte: Where Bacteria And Diet Meet, Bohye Park

Doctoral Dissertations

The host-microbiome interaction and the functions of microbial-derived metabolites, including butyrate, are important in colon health. Butyrate is the preferred energy source in colonocytes and has multiple physiological functions in the colon. A metabolic shift in colonocytes toward increased glucose utilization from butyrate oxidation is followed by several critical genetic modifications in cancerous colonocytes. Moreover, it has been suggested that the gut-microbiota composition is influenced by environmental factors, such as diets and the host's physiological status. Therefore, an understanding of the role of colonocyte metabolism toward impacting the host-microbiota commensal relationship would be an important step in understanding the ...

Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna

Graduate Theses and Dissertations

The Ras superfamily of small G proteins are involved in cell-signaling processes that, if not regulated, may lead to cell multiplication, apoptosis inhibition, and tumorigenesis. They function as molecular switches, which through GTP/GDP exchange cycle, switch on or off cellular activities. Overexpression and/or hyperactivity of these proteins have been linked to many diseases including various cancers. CDC42, a member of the Rho subfamily of the Ras superfamily of small G proteins, participates in the regulation of many cellular processes including cell adhesion, mitosis, and cytoskeletal rearrangements. CDC42 binds to and activates many effector proteins including CDC42-activated kinase (ACK ...

Headcase Regulates Growth In Response To Nutritional Status Downstream Of Insulin Signaling, Thomas George

Honors Scholar Theses

Cancer cells are notorious for growing in an unrestricted manner without regard for environmental cues. Recently, Li et al. (2019) discovered headcase (hdc) functions by binding to the mTORC1 complex in the mTOR signaling pathway and preventing further signaling. Interestingly, under nutrient restricted (NR) conditions, cells with mutated hdc proteins proliferated more than cells with normal functioning hdc. It is well known that insulin signaling is downregulated under NR conditions, so a potential signaling pathway with insulin, PI3K, PDK1, Akt, PTEN, and hdc was created as a way to explain the link between hdc function and nutritional status. A Drosophila ...

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We ...

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the ...

Methods For Assessing Cellular Phenotypes Related To Aging And Longevity In Turtles, Stephanie E. Bulls

Theses and Dissertations

There are many costs associated with increased body size and longevity in animals, including the accumulation of genotoxic and cytotoxic damage that comes with having more cells and living longer. Yet, some species have overcome these barriers and have evolved remarkably large body sizes and long lifespans. Organisms with these unique phenotypes have come under recent genomic scrutiny to discover mechanisms of healthy aging and tumor suppression but little physiological work to validate these mechanisms has been conducted outside of mammals. Here I propose that reptiles, especially testudines (turtles), would be an excellent system to investigate the topics of size ...