Cancer Biology Commons^™

Usefulness Of Circulating Tumor Dna In Identifying Somatic Mutations And Tracking Tumor Evolution In Patients With Non-Small Cell Lung Cancer, Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Hatim Husain, Karen L. Reckamp, Marianna Koczywas, Erminia Massarelli, Andrea H. Bild, Ravi Salgia

Pharmacy Faculty Articles and Research

Background

The usefulness of circulating tumor DNA (ctDNA) in detecting mutations and monitoring treatment response has not been well studied beyond a few actionable biomarkers in non-small cell lung cancer (NSCLC).

Research Question

How does the usefulness of ctDNA analysis compare with that of solid tumor biopsy analysis in patients with NSCLC?

Methods

We retrospectively evaluated 370 adult patients with NSCLC treated at the City of Hope between November 2015 and August 2019 to assess the usefulness of ctDNA in mutation identification, survival, concordance with matched tissue samples in 32 genes, and tumor evolution.

Results

A total of 1,688 somatic …

Role Of Ampk And Akt In Triple Negative Breast Cancer Lung Colonization, Jeremy Johnson, Zeta Chow, Eun Young Lee, Heidi L. Weiss, B. Mark Evers, Piotr G. Rychahou

Pathology and Laboratory Medicine Faculty Publications

Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 …

Toxic Effect Of Crotalus Adamanteus Acidic Phospholipase A2 On Mcf-7 Cell Line, Daniel J. Petra

Honors Thesis

We are investigating the effect of Crotalus adamanteus acidic phospholipase A₂ on MCF-7 cells using the MTS assay. Understanding these interactions and isolated effects is critical to developing new ways to treat envenomation. By understanding the effects of individual toxins within a whole venom, we are set to better understand the effects of the whole venom and investigate synergistic actions between venom toxins. In this paper, we are quantifying the amount of MCF-7 cell death caused by Crotalus adamanteus phospholipase A₂ on MCF-7 using the MTS assay. Analysis of the amount of cells death caused by the phospholipase …

Redefining Cancer Of Unknown Primary: Is Precision Medicine Really Shifting The Paradigm?, Timothée Olivier, Eugenio Fernandez, Intidhar Labidi-Galy, Pierre-Yves Dietrich, Veronica Rodriguez-Bravo, Giulia Baciarello, Karim Fizazi, Anna Patrikidou

Department of Cancer Biology Faculty Papers

The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group. CUP features significant oncological challenges, such as unravelling biological and transversal issues, and most importantly, improving patient's outcomes. In that regard, CUP patients’ outcomes regrettably showed minimal improvement for decades and CUP remains a cancer group of very poor prognosis. The biology …

The Effects Of A Survivorship Care Plan On Hospital Readmission Rates In Allogenic Stem Cell Transplant Patients, Chantaney Williams

The Eleanor Mann School of Nursing DNP Capstone Projects

Stem cell transplants (SCTs) are complicated treatments utilized to treat hematologic malignancies and other disorders, such as multiple myeloma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, acute myeloid leukemia, neuroblastomas, germ cell tumors, amyloidosis, and autoimmune disorders such as systemic lupus erythematosus and systemic sclerosis. The complex care of patients undergoing SCTs place them at high risk for adverse outcomes, including infection, cytomegalovirus, graft vs host disease, secondary new cancers, infertility, and sexual dysfunction (American Cancer Society, 2020). Survivorship care plans (SCPs) are a vital part of the discharge process to educate allogenic SCT patients about post-transplantation care. SCPs are implemented to reduce …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

Identifying Determinants Of Breast Cancer Screening Through Mammography Among Asian American Women, Sayeda Tazim Zaidi, Raisa Kabir, Chia-Liang Dai

Undergraduate Research Symposium Posters

Breast cancer is the most common malignancy affecting women around the world. In the US, approximately 1 in 8 women will develop breast cancer over the course of their lifetime. There is a growing incidence of breast cancer among Asian American (AA) women. Breast cancer screening by mammography is the most effective early detection method to reduce mortality but AA women have the lowest utilization rates. This study aims to identify the determinants affecting mammography among AA women. A literature search in PubMed Central, MEDLINE, and CINAHL was undertaken to include all peer-reviewed studies published within the past 20 years …

Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark

Honors College Theses

Metastasis- the spread of cancer cells from the primary tumor to the surrounding tissues- is responsible for 90% of cancer deaths. Integrin alpha-6 (ITGA6) is a specific transmembrane cell surface protein that functions in cell surface adhesion and signaling. ITGA6 is upregulated in many types of cancers and promotes the migration and invasion of cancer cells to surrounding tissues. It is my objective to determine the mechanism through which ITGA6 facilitates the migration of cancer cells through the extracellular matrix (ECM). These experiments helped to establish the role of ITGA6 in tumor development and provide focus for possible chemotherapeutic treatment. …

Expression And Function Of Transcription Factors Foxa1, Hoxb13 And Cdx2 In Prostate Cancer, Hamsat B. Anwar

University Honors Theses

Prostate cancer (PC) is the second leading cause of death in men, affecting around 190 thousand patients in 2020 alone (National Institute of Cancer, 2020). Much of the current research focuses on treatments for advanced PC, which is problematic due to the rapid evolution of tumors and development of treatment resistance. Cancer early detection presents a better approach to control and treat patients before they acquire an incurable disease. Earlier diagnosis of patients leads to better prognosis and a more comfortable treatment process (Etzioni et al., 2003). However, we currently lack molecular markers to stratify PC during its early stages. …

Dna Repair Pathways In Cancer Therapy And Resistance, Lan-Ya Li, Yi-Di Guan, Xi-Sha Chen, Jin-Ming Yang, Yan Cheng

Toxicology and Cancer Biology Faculty Publications

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for …

Evaluation Of Triclosan Exposures On Secretion Of Pro-Inflammatory Cytokines From Human Immune Cells, Wendy J. Wilburn, Sara Jamal, Farah Ismail, Dylan Brooks, Margaret Whalen

Chemistry Faculty Research

Triclosan (TCS) is widely used in personal hygiene products, such as mouthwash and toothpaste, and is found in human tissues. Interleukin (IL)-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) are pro-inflammatory cytokines and inappropriately elevated levels of each have been associated with pathologies including rheumatoid arthritis and certain cancers. Here we examine effects of TCS on the secretion of the pro-inflammatory cytokines from human immune cell preparations. TCS at concentrations between 0.05–5 μM consistently increased the secretion of IL-1β, IL-6, and TNFα within 24 h of exposure and the increases often maintained out to 6 …

Macrophage And Adipocyte Interaction As A Source Of Inflammation In Kidney Disease, Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, D. Craig Hooper, Bonita Falkner, Maria P Martinez Cantarin

Kimmel Cancer Center Faculty Papers

In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue …

Evaluation Of The Anticancer Potential Of Alchemilla Vulgaris Extract Against Human Neuroblastoma Cells, Yomna Moqidem

Theses and Dissertations

Neuroblastoma is one of the most challenging pediatric tumors that present heterogeneity in prognosis and survival despite intensive treatment protocols. Therefore, there is an urge to develop novel and more potent anticancer drugs. Medicinal plants have recently gained worldwide attention due to their variable activities, wide availability, and cost-efficiency. Accordingly, this study attempted to identify novel plant extracts that could show potential anticancer properties against neuroblastoma. In this study, Alchemilla vulgaris (A.vulgaris) ethyl acetate extract was prepared and evaluated for its anticancer potential against SH-SY5Y Human neuroblastoma cell line. The Phenolic content of the prepared extract was characterized …

Cell Cycle Progression Effects Of Albumin, Sharmeen Uddin

Dissertations, Theses, and Capstone Projects

Progression through G₁ phase of the cell cycle is controlled largely by growth factors in early G₁ and by nutrients in late G₁ indicating sufficient raw material for cell division. We previously mapped a late G₁ cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G₁ checkpoint known as the Restriction point. We therefore investigated a role for lipids in progression through late G₁ into S-phase. Quiescent BJ-hTERT human fibroblasts primed back into G1 with FBS treatment, were treated with a mixture of …

Differential Expression Of Αvβ3 And Αvβ6 Integrins In Prostate Cancer Progression, Fabio Quaglia, Shiv Ram Krishn, Yanqing Wang, David W Goodrich, Peter Mccue, Andrew Kossenkov, Amy C Mandigo, Karen Knudsen, Paul H Weinreb, Eva Corey, William Kevin Kelly, Lucia R Languino

Department of Cancer Biology Faculty Papers

Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined αVβ3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

The Circadian Cryptochrome, Cry1, Is A Pro-Tumorigenic Factor That Rhythmically Modulates Dna Repair., Ayesha A Shafi, Chris M Mcnair, Jennifer J Mccann, Mohammed Alshalalfa, Anton Shostak, Tesa M Severson, Yanyun Zhu, Andre Bergman, Nicolas Gordon, Amy C Mandigo, Saswati N Chand, Peter Gallagher, Emanuela Dylgjeri, Talya S Laufer, Irina A Vasilevskaya, Matthew J Schiewer, Michael Brunner, Felix Y Feng, Wilbert Zwart, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required …

Propranolol Sensitizes Vascular Sarcoma Cells To Doxorubicin By Altering Lysosomal Drug Sequestration And Drug Efflux, Jhuma Saha, Jong Hyuk Kim, Clarissa N. Amaya, Caleb M. Witcher, Ali Khammanivong, Derek M. Korpela, David R. Brown, Josephine Taylor, Brad A. Bryan, Erin B. Dickerson

Faculty Publications

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and …

Crippling Rapid Evolution Of Metastasis And Drug Resistance In A549 Non-Small Cell Lung Cancer Cells With The Clinically Relevant Hsp90 Inhibitor Auy922, Nickolas Anthony Bacon

Theses, Dissertations and Capstones

The ability for species to evolve new features in response to changing circumstances in order to survive and propagate is a ubiquitous observation on both the macroscopic and microscopic levels of living systems. It should be no surprise, then, that diseases such as cancer utilize their own forms of adaptation to perpetuate themselves when exposed to external threats. Indeed, concepts drawn from Darwinian evolution are now widely accepted to help explain certain aspects of carcinogenesis and malignant progression, the sum of which have come to be known as the theory of tumor evolution. Since metastasis and drug resistance are features …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Effect Of He Plasma Jet Versus Surface Plasma On The Metabolites Of Acute Myeloid Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Wenjie Xia, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and …

Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral

Theses and Dissertations--Pharmacy

Immune checkpoint inhibitors (ICIs), especially those that target programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), have been shown to provide substantial clinical benefit in many patients with non-small cell lung cancer (NSCLC). While these therapeutic agents can be highly effective in the correct context, the biological systems that malignant cells draft from normal activities of the cell are poorly characterized. Tumor cell-specific expression of PD-L1 is likely important for clinical benefit from PD-1 and PD-L1 inhibitors. It is known that PD-L1 is inappropriately expressed in many cancers harboring mutations in the RAS family of genes. …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

Bacterial Association Networks From Healthy And Cancer-Associated Gut Microbiomes, Mark Loftus

Electronic Theses and Dissertations, 2020-2023

The human gastrointestinal tract is colonized by a diverse community of symbiotic microorganisms, mainly bacteria, that are known to play essential roles in maintaining the health of their human host. Disruption of this bacterial community has been associated with numerous diseases, including Colorectal Cancer (CRC). CRC is one of the leading causes of cancer-related deaths worldwide. As such, focus has been placed on the modulation of the bacterial community within the cancer-associated gut microbiome as the next step in possible CRC treatment and prevention strategies. To use the bacterial community for these purposes, a better understanding of the associations that …

Therapeutic Targeting Of Leukemia Stem Cells To Prevent T-Cell Acute Lymphoblastic Leukemia Relapse, Meghan G. Haney

Theses and Dissertations--Molecular and Cellular Biochemistry

The survival rate of T-cell Acute Lymphoblastic Leukemia (T-ALL) relapse is a dismal 10% of affected adults and 30% of children, largely due to the relapsed disease being more aggressive and treatment resistant than the initial disease. Relapse is thought to occur because conventional chemotherapies are unable to reliably eliminate a unique cell type known as leukemia stem (or propagating) cells (LSCs). LSCs are the only cells within the leukemia with the ability to self-renew and remake or replenish the ALL from a single cell. Currently, the pathways governing self-renewal in LSCs are largely unknown, precluding our ability to successfully …

Association Of Palb2 Variants With Risk To Breast Cancer And Molecular Characterisation Of Palb2 Tumours, Ng Pei Sze

Student Works (2020-2029)

Purpose: Germline rare protein truncating variants (PTVs) in PALB2 are associated with an increased risk to breast cancer. At present, most of the available data on genetic predisposition to breast cancer are derived from studies in women of European descent, and it is unclear the extent to which population-specific differences in genetic and lifestyle factors may contribute to differences in lifetime risk to breast cancer in women of other ancestries. This study sought to determine the prevalence of, mutation spectrum in and the risk estimates associated with PALB2 in a multiethnic cohort of 7840 breast cancer cases and 7928 healthy …

The Therapeutic Potential Of Glycosaminoglycan Directed Metalloglycomics: Elucidating New Targets And Mechanisms For Polynuclear Platinum Complexes, James D. Hampton

Theses and Dissertations

Cancer remains a serious clinical problem and in order to continue to improve patient health outcomes, novel treatment strategies must continue to be developed. Platinum chemotherapies remain as one of the most widely successful classes of cancer therapeutic, with over 50% of cancer patients receiving a platinate at some point over the span of their treatment. However, intrinsic and extrinsic resistances limit their effectiveness, long term efficacy, and broad applicability to multiple cancer subtypes. Therefore, the development of new agents and strategies which can overcome these limitations are crucial for patient health. To this end a novel class of polynuclear …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

Plasma-Treated Solutions (Pts) In Cancer Therapy, Hiromasa Tanaka, Sander Bekeschus, Dayun Yan, Masaru Hori, Michael Keidar, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …