Medical Sciences Commons^™

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie

Masters Theses

Retinoblastoma is the leading cause of intraocular malignancy in children under 2 years of age. Current treatments, while generally effective in eliminating the tumor, have many negative side effects. Oncolytic virotherapy is the use of either wild type or recombinant viruses, to destroy tumor cells. There are currently several viruses being engineered as potential therapeutics for a wide range of cancers. They offer tumor specific alternative to current therapies with lesser toxicity. This study looked at the oncolytic efficacy of multiple tanapoxviruses (TPV) recombinants in an in vitro retinoblastoma. Here we have tested recombinants of TPV for their ability to …

Current And Emerging Uses Of Statins In Clinical Therapeutics: A Review, Jonathan T. Davies, Spencer F. Delfino, Chad E. Feinberg, Meghan F. Johnson, Veronica L. Nappi, Joshua T. Olinger, Anthony P. Schwab, Hollie I. Swanson

Pharmacology and Nutritional Sciences Faculty Publications

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin …

Targeted And Controlled Anticancer Drug Delivery And Release With Magnetoelectric Nanoparticles, Alexandra Rodzinski

FIU Electronic Theses and Dissertations

A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Franklin D. Shuler

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K2 (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation of …

An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey

Jarrod Bailey, PhD

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Marshall Journal of Medicine

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K₂ (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation …

Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz

Theses and Dissertations (ETD)

Pediatric high-grade gliomas (pHGGs), with a two-year survival rate of less than 20%, are some of the most aggressive human cancers. This dissertation begins with our analysis of 127 pHGGs, including brainstem (BS) and non-brainstem (NBS) tumors, from 118 patients using next-generation sequencing technologies. Nearly one-third of BS-HGGs, also known as diffuse intrinsic pontine gliomas (DIPGs), harbored somatic heterozygous missense mutations in ACVR1, coding for a receptor serine-threonine kinase involved in bone morphogenetic protein (BMP) signaling. These alterations led to gain-of-function as evidenced by increased phosphorylation of downstream targets in primary astrocytes and zebrafish embryo ventralization. Whole-genome sequencing and …

The Effect Of Luteolin On Human Glioblastoma, David M. Anson, Samson Amos, Robert L. Paris, Denise S. Simpson

The Research and Scholarship Symposium (2013-2019)

Glioblastoma multiforme (GBM) is widely recognized as the most common and lethal of the malignant gliomas. Few effective therapeutic treatments are available as five-year survival rates of diagnosed individuals are less than five percent. Luteolin, a common flavonoid found in a variety of fruits and vegetables, has demonstrated significant promise in combating cancers of the breast, colon, liver, lung, and bone. In this study, we investigated the effects of luteolin on glioblastoma multiforme cell lines U-251, U-87, and U-1242. Cell viability was assessed using cell count with trypan blue exclusion and MTT assays. Results revealed that luteolin reduces GBM cell …

Synthesis And Characterization Of Nanoparticle-Coupled Proteins In Human Serum Albumin, Kyle M. Mahoney

Honors College Theses

Recently, cancer has become an ever-growing issue and has led to many researchers attempt to unravel the mystery of the disease. This research has led to a promising field of treatment: nanotechnology-coupled pharmaceuticals. Nanoparticles act as a whole unit when in conjugation with other molecules and add to the carrier molecule, most often proteins, benefits the nanoparticles themselves possess. One such carrier protein that can be conjugated with nanoparticles is Human Serum Albumin (HSA). Albumin is of interest in cancer research for two reasons: it is native to the human vasculature so it does not elicit immunological reactions, and it …

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8⁺ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …

The Effect Of Enteral Immunonutrition In Upper Gastrointestinalsurgery For Cancer: A Prospective Study, Seli̇m Yi̇ği̇t Yildiz, Murat Burç Yazicioğlu, Çağri Ti̇ryaki̇, Ali̇ Çi̇ftçi̇, Zehra Boyacioğlu, Mehmet Özyildiz, Murat Coşkun, Özkan Subaşi

Turkish Journal of Medical Sciences

Background/aim: Enteral feeding and immunonutrition (ImN) have been shown to be associated with a number of favorable effects in patients undergoing cancer surgery. In this prospective study, we aimed to assess the perioperative use of enteral immunonutrition in patients undergoing radical gastrointestinal surgery for malignancy. Materials and methods: Forty-one patients with malignancy were included in this study and were randomized into one of the two following nutritional strategies: enteral only (EN) or enteral with enteral immunonutrition (ENIN). These regimens were followed for 7 days perioperatively by all patients. Nutritional parameters and postoperative morbidity, mortality, and length of hospital stay (LHS) …

Epidemiology And Cost Of Drug Treatment Of Cancer In Northern Cyprus, Ayşe Gökyi̇ği̇t, Seyi̇de Rumeysa Demi̇rdamar

Turkish Journal of Medical Sciences

Background/aim: To determine the epidemiology, the sociodemographic features, the incidence and prevalence rate of cancer, and the cost of drug treatment in Northern Cyprus. Materials and methods: All of the oncology prescriptions, cancer pathology reports, and cancer referrals to overseas for 2011 were collected from the state hospitals, the only private university hospital that provides oncology services, and the Ministry of Health to prepare an epidemiological database. The total cost of drug treatment at the state hospitals and cost of the most frequent five cancer types were also calculated using the therapy protocols and the expense of the drugs. Results: …

The Incidence Of 18f-Fdg Pet/Ct Thyroid Incidentalomas Andthe Prevalence Of Malignancy: A Prospective Study, Mi̇ne Şencan Eren, Özhan Özdoğan, Arzu Gedi̇k, Mehmet Ceylan, Meri̇h Güray Durak, Mustafa Seçi̇l, Mehmet Ali̇ Koçdor, Abdurrahman Çömlekçi̇, Hati̇ce Durak

Turkish Journal of Medical Sciences

Background/aim: To determine the prevalence of malignancy in thyroid incidentalomas (TIs) detected by fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). Materials and methods: 18F-FDG PET/CT images were evaluated prospectively for the presence of thyroid uptake. The patients with a TI were evaluated by an endocrinologist according to the predefined diagnostic algorithm. The final diagnosis was obtained clinically and/or by pathology. Results: TI was detected in 4.2% of 4204 patients. A malignant thyroid nodule was diagnosed in 29% and 33% of the focal and diffuse-focal uptake groups, respectively. However, no malignancy was detected in the diffuse uptake group. The standardized …

Pacaha Inhibits Proliferation Of Human Cancer Cells In Vitro, Sali̇ha Ekşi̇, Nebahat Ejder, Fati̇h Yilmaz, Ayşe Ertürk, Cemal Sandalli

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to investigate the antiproliferative and cytotoxic effects of a newly synthesized molecule named paracetamol acetohydroxamic acid (PaCaHa) on human neoplastic cell lines. Materials and methods: A549, CRL 2923, HeLa, and ARPE were treated with various concentrations of PaCaHa and DMSO (vehicle control). The cytotoxic/cytostatic effects of PaCaHa were determined after a 24-h incubation period and compared to the DMSO control. The cytotoxic and antiproliferative effects were determined by the trypan blue dye exclusion and MTT methods. Results: A higher susceptibility to PaCaHA was found in CRL 2923 and HeLa cells, while A549 and …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Prostate Cancer: Screening, Current Guidelines And Patient Education, Timothy F. Flanagan

Family Medicine Clerkship Student Projects

Recent changes in prostate cancer screening guidelines may create an opportunity for patient education. By creating a succinct hand-out on prostate cancer screening, providers enable their patients to understand screening, and provide sites with opportunities for further learning.

Management Of Acute Postoperative Hypertension For Reducing Cardiovascular Complications In Cancer Patients: When And How Aggressively?, Ning Lou, Daofeng Wang, Zhi Wang, Wenfeng Ye, Xiao Liu

Turkish Journal of Medical Sciences

Background/aim: We sought to determine what factors cardiovascular complications (CVCs) correlate with in cancer patients with acute postoperative hypertension (APH) and to define when and how aggressively to treat this disorder in the present study. Materials and methods: A retrospective observational study of cancer patients with postoperative hypertension at a single intensive care unit between July 2007 and June 2013 was conducted. The outcome of interest was the incidence of a CVC. Results: There were 1162 patients enrolled, of which 92 (7.9%) experienced one or more CVCs. Preexisting hypertension (OR 38.3, 95% CI 3.2-457.4, P = 0.004) and choice of …

Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell

All ETDs from UAB

It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …