Medicine and Health Sciences Commons^™

Targeting Dusps In Glioblastomas–Wielding A Double‐Edged Sword, Sheila Abraham, Swapna Asuthkar, William Lee, Srinivasulu Chigurupat, Andrew Tsung, Kiran Kiran

Sheila Prabhakar Abraham

Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

The Effect Of An Educational Intervention On Knowledge And Intent To Participate In Cervical Cancer Screening, Ann Marie Trapp

Evidence-Based Practice Project Reports

Globally, cervical cancer ranks third among cancers affecting women (Arbyn et al., 2013). In the United States, approximately 12,000 women are diagnosed with cervical cancer and approximately 4,000 women die yearly (Centers for Disease Control and Prevention, 2014). Papanicolaou (Pap) screening is an effective means of detecting precancerous cell changes of the cervix with early cervical cancer diagnosis carrying a 91% five-year survival rate (Gonzalez et al., 2012). The purpose of this evidence-based practice project was to identify interventions that increase adherence to cervical cancer screening and to implement best practices to reduce unnecessary deaths related to late diagnoses of …

Active Immunotherapy And Adoptive Cell Transfer As An Effective Cancer Treatment, Philip Jay Cynamon

The Science Journal of the Lander College of Arts and Sciences

There are many ways to fight cancer using the body’s own immune system. Some methods include the administration of vaccines while others involve stimulatory factors injected near tumors. One promising method is enlisting the help of T cells. To fight cancer effectively, T cells must be able to recognize cancerous antigens and the environment in which these T cells reside must be conducive to their function, survival, and proliferation. This paper discusses a method of providing such an environment called adoptive cell transfer, as well as the elements that effect this protocol and the ways in which the environment can …

Epigenetics As A Cure For Cancer, Sara Rivka Margolis

The Science Journal of the Lander College of Arts and Sciences

Epigenetics is an emerging research topic that is being tested as a potential cure for cancer. Epigenetics is a non-genetic influence that shapes the phenotype. Epigenetics effects gene expression, but does not cause any changes in the DNA. DNA methylation patterns is one such epigenetic change in the cell that has huge potential for cancer treatment. Scientists have observed that many cancerous genes express signs of either hypermethylation or hypomethylation. The key for the treatment is that epigenetic changes are reversible, which opens the door to potential drugs to cure cancer and other diseases.

Why Are People With Laron Syndrome Immune To Cancer?, Raquel Margolis

The Science Journal of the Lander College of Arts and Sciences

Laron syndrome is a congenital autosomal recessive disorder that is caused by a mutation in the growth hormone receptor. People with this syndrome have an insensitivity to growth hormone. Insulin-like growth factor 1 is produced by the liver in response to GH stimulus. It is responsible for systemic GH activities. If there is something wrong with the growth hormone receptor there will be decreased levels of IGF-1. Low IGF-1 levels cause physical deformities notable short stature. Additionally, people with low levels of IGF-1 have a natural resistance to cancer. This article discusses the ways that the decreased levels of IGF-1 …

Transposon Based Gene Therapy As A Treatment For Cancer, Jacob Stauber

The Science Journal of the Lander College of Arts and Sciences

Gene therapy is the use of genes to treat or prevent diseases. Diseases such as cancer, which are difficult to treat using conventional methods, can be treated using gene therapy. The transport of the therapeutic transgene can be accomplished using viral or non-viral methods. However, widespread use of viral vectors is limited due to its high cost of manufacture and safety concern. Non-viral vectors are limited in their effectiveness. The use of transposons such as the Sleeping Beauty transposon system can effectively deliver the transgene with less concern than viral vectors. This review discusses the various vectors and treatment strategies …

Cancer Stem Cells In The Screening Of Anticancer Drugs For Central Nervous System Tumors, Sarah Elizabeth Daron-Mathis

Theses, Dissertations and Capstones

There is a growing need (in the medical field) to design personalized therapy for cancer patients. Decades of cancer research have found no silver bullet that can cure all or even most patients. This study evaluated four patients affected by central nervous system (CNS) tumors (Ependymoma and Glioblastoma), and found that tumors with the same histology had unique responses to treatment. Each sample presented different levels of heterogeneity in expressed biomarkers and responded to drugs at varying levels.

Oncologists conventionally treat cancer patients with drugs tested in large clinical trials. However, often patients do not experience positive outcomes following treatments …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Curcumin: A Folklore Remedy From Kitchen On The Way To Clinic As Cancer Drug, Debasish Bandyopadhyay

Chemistry Faculty Publications and Presentations

Numerous compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, …

Killing Adherent And Nonadherent Cancer Cells With The Plasma Pencil, Mounir Laroussi, Soheila Mohades, Nazir Barekzi

Electrical & Computer Engineering Faculty Publications

The application of low temperature plasmas in biology and medicine may lead to a paradigm shift in the way various diseases can be treated without serious side effects. Low temperature plasmas generated in gas mixtures that contain oxygen or air produce several chemically reactive species that have important biological implications when they interact with eukaryotic or prokaryotic cells. Here, a review of the effects of low temperature plasma generated by the plasma pencil on different cancerous cells is presented. Results indicate that plasma consistently shows a delayed killing effect that is dose dependent. In addition, there is some evidence that …

Interaction Of Disease, Drugs, And Disposition In Ewing's Sarcoma Patients, Madeline Martin

Honors Theses

Ewing's Sarcoma is a pediatric bone cancer that is highly aggressive, leading to a five year survival rate of not only 30% even with multi-modal treatment protocols. Improved therapeutic options are desperately needed. Our research has focused on the ability of the psychoactive cannabinoid, ajulemic acid, to induce apoptosis and decrease metastatic potential in cells from members of the Ewing Sarcoma family of tumors. Recently, we explored the effects of the naturally-occuring cannabinoid, cannabidiol, on three-dimensional spheroids that mimic the cellular components and microenvironment of Ewing's tumors. We looked at how this treatment affects VEGF, a mediator of angiogenesis, to …

The Effect Of Cannabinoids On Triple Negative Breast Cancer Cells, Haley Dahl

Honors Theses

Triple Negative Breast Cancer (TNBC) is a difficult type of cancer to treat because it is negative for progesterone, estrogen, and HER-2 receptors. Because TNBC is negative for these three receptors, it does not respond to normal hormonal therapies. The purpose of my experiment is to see if different cannabinoids, compounds from the cannabis plants, could be used as alternative treatment options. These experiments employed three different cannabinoids: ajulemic acid, cannabidiol, and hemp oil. Cell viability was measured after 72 hours of treatment using a MTT assay. The results showed that the three cannabinoids could be used to effectively destroy …

Acute Promyelocytic Leukemia As A Possible Source For Ajulemic Acid Binding, Brian Christopher Monk

Honors Theses

Acute promyelocytic leukemia (APL) is a cancer that affects bone marrow, the blood-forming tissue (of the body). This type of leukemia accounts for approximately 10% of acute myeloid leukemia (AML) cases. Normally this cancer is treated with a drug called all-trans retinoic acid (ATRA), but other variations of treatment do exist. The importance of this research is that APL cells express contains a receptor, retinoic acid receptor-a (RARa), which ajulemic acid (AJA) may bind to in order to induce apoptosis in Ewing sarcoma (ES), a pediatric bone cancer. Therefore, this research will focus on the ability of AJA to induce …

Drug-Induced Cardiotoxicity Of Oncological Agents: Monitoring Parameters, Prevention, And Future Chemotherapy, Sarah Nguyen, Mary Nguyen, Laura Tsu

Pharmacy Faculty Articles and Research

The goal of this article is to educate pharmacists of the impact of cardiotoxicity on chemotherapy regimens including key cancer agents, monitoring parameters, prevention, and the future of chemotherapy.

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …