Neoplasms Commons^™

Is Tamoxifen Prophylaxis Effective In Reducing The Incidence Of Breast Cancer In Women Who Are At High Risk?, Maria Deveau

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this EBM review is to determine whether or not Tamoxifen prophylaxis is effective in reducing the incidence of breast cancer in woman who are at high risk.

STUDY DESIGN: Review of three English language primary studies published from 2005 to 2007.

DATA SOURCE: Three double-blind randomized control trials found using the PubMed and Cochrane database.

OUTCOME MEASURED: The primary outcome by all three studies included incidence of breast cancer.

RESULTS: Three double- blind randomized controlled trials were included in this review. Study by Powles et al showed statistically significant reduction in the incidents of breast cancer …

Is Temozolomide In Combination With Interferon Alpha-2b A Safe And Effective Treatment For Malignant Melanoma?, Kathleen Vincento

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not temozolomide in combination with interferon alpha-2b a safe and effective treatment for malignant melanoma.

Study Design: Review of three randomized controlled trials published in the United States and Britain between 2003 and 2005.

Data Sources: Three non-blind randomized controlled trials were found via Cochrane library and PubMed.

Outcomes Measured: Efficacy was measured by survival greater than or equal to 12 months, with one (experimental) group receiving treatment with oral temozolomide (TMZ) and subcutaneous interferon alpha-2b (IFN-∝2b) and the other (control) group receiving oral TMZ alone. Safety …

Do Braf Inhibitors Improve Survival In Patients With Braf V600e Mutant Melanoma?, Sarah E. Stamm

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Do BRAF inhibitors improve survival in patients with BRAF V600E mutant melanoma?”

STUDY DESIGN: Review of primary literature sources that examined survival rates in BRAF V600E mutant melanoma patients receiving treatment with a BRAF inhibitor.

DATA SOURCES: Two randomized controlled trials and one cohort study evaluating the use of BRAF inhibitors in patients with BRAF V600E mutant melanoma were found using OVID, Medline, and PubMed.

OUTCOMES MEASURED: Overall survival and progression free survival were the outcomes measured to determine survival rates in patients with BRAF V600E …

Is Pomalidomide Plus Low Dose Dexamethasone An Effective And Safe Treatment For Patients With Relapsed Or Refractory Multiple Myeloma?, Matthew Westervelt

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not pomalidomide plus low dose Dexamethasone is an effective and safe treatment for patients with relapsed or refractory multiple myeloma (RRMM).

Study Design: Review of three open-label clinical trials with one published in 2012 and two published in 2013.

Data Sources: Two randomized, open-label, phase 2 clinical trials and one open-label phase 3 clinical trial evaluating efficacy of pomalidomide plus low dose dexamethasone and its safety were found using the PubMed database.

Outcomes Measured: Efficacy of pomalidomide plus low-dose dexamethasone was measured by overall response rates (ORR) …

Web Tool For Estimating The Cancer Hazard Rates In Aging., Tengiz Mdzinarishvili, Alexander Sherman, Oleg Shats, Simon Sherman

Journal Articles: Eppley Institute

A computational approach for estimating the overall, population, and individual cancer hazard rates was developed. The population rates characterize a risk of getting cancer of a specific site/type, occurring within an age-specific group of individuals from a specified population during a distinct time period. The individual rates characterize an analogous risk but only for the individuals susceptible to cancer. The approach uses a novel regularization and anchoring technique to solve an identifiability problem that occurs while determining the age, period, and cohort (APC) effects. These effects are used to estimate the overall rate, and to estimate the population and individual …

Overcoming Barriers To Screening For Anal Intraepithelial Neoplasia For Persons Living With Hiv, Brandon Hastings

Doctor of Nursing Practice (DNP) Projects

Screening has proven an effective strategy in the management of diseases that plague the population. This technique has proven to be most effective when screening is conducted with those who are most at risk for developing the targeted illness and when the frequency of screening follows set guidelines. Currently there are no nationally recognized screening guidelines for anal intraepithelial neoplasia (AIN). Screening for AIN stands to reduce overall incidence of anal squamous cell carcinoma through destruction of the dysplastic cells before they become cancerous. The goals of this project were to identify the patient population that stands to benefit the …

E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung

Dartmouth Scholarship

Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score …

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …

Autoantibodies To The Ny-Eso-1 Tumor Antigen In Metastatic Melanoma: Sialylation Of The Fc Region Of Immunoglobulin G Induces Differential Expression Signatures Of Inflammatory Molecules During Dendritic Cell Differentiation And Maturation, Martin Oaks, Nathaniel Rein, John O. Richards, James Shaffer

Journal of Patient-Centered Research and Reviews

Purpose: We tested the hypothesis that different glycoforms of antibodies from patients with metastatic melanoma have different functional effects on human dendritic cell differentiation and maturation.

Methods: Antibodies to the cancer antigen NY-ESO-1 were affinity-purified from patients with melanoma and further fractionated into different glycoforms by lectin chromatography. Sialic acid-rich and sialic acid-poor fractions of these immunoglobulin G antibodies (IgG) were added to dendritic cell cultures during both differentiation and maturation, and the resulting cellular messenger RNA (mRNA) and culture supernatants were tested by microarray and enzyme-linked immunoassay for molecules related to inflammatory pathways.

Results: We identified unique mRNA and …

Novel Biomarkers Can Be Used As Targets To Combat Cancer, Harini Krishnan

Graduate School of Biomedical Sciences Theses and Dissertations

Cancer kills almost 8 million people per year worldwide. Therefore, about 13 people die from cancer every minute. Clearly, current cancer treatments are not completely effective. Moreover, many chemotherapeutic reagents are not very specific for cancer cells.

These agents attack rapidly dividing cells, including a wide array of normal cells, in addition to cancer cells, in the body. This lack of specificity can cause collateral damage and significant side effects in patients. More targeted therapies are needed to successfully combat cancer. Specific cancer biomarkers need to identified and characterized in order to develop better targeted anti-cancer drugs.

Tumor cells can …

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …

Pathophysiology, Incidence And Implications In Intraductal Papillary Mucinous Neoplasia Of The Pancreas, Ericka Haverick

Nursing Student Class Projects (Formerly MSN)

Intraductal papillary mucinous neoplasms (IPMN) are uncommon tumors arising from the main pancreatic duct, branching pancreatic ducts, or both. The “overall incidence of invasive carcinoma associated with resected IPMN has been reported to be 20-40%” (Mohri et al., 2011). Due to their malignant potential, these lesions, along with mucinous cystic neoplasms (MCN), are considered more worrisome, and often require surgical resection (Gallucci, Langellotto, De Ritis, & Uomo, 2012). Even after removal of a primary lesion, patients remain under surveillance to monitor for recurrence, the rate of which is approximately 6 % (Gallucci et al., 2012), and patients with main duct …

Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov

Dartmouth Scholarship

INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.

We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine …

Nack Is An Integral Component Of The Notch Transcriptional Activation Complex And Is Critical For Development And Tumorigenesis, Kelly L Weaver, Marie-Clotilde Alves-Guerra, Ke Jin, Zhiqiang Wang, Xiaoqing Han, Prathibha Ranganathan, Xiaoxia Zhu, Thiago Dasilva, Wei Liu, Francesca Ratti, Renee M Demarest, Cristos Tzimas, Meghan Rice, Rodrigo Vasquez-Del Carpio, Nadia Dahmane, David J Robbins, Anthony J Capobianco

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are …

An Uncommon Presentation For Cardiac Melanoma, Burcu Gul, Michael N. Young, David A. Slosky, Mark A. Lawson, Jeffrey N. Rottman

Journal of Patient-Centered Research and Reviews

A 66-year-old man with locally advanced malignant melanoma, which was surgically resected, presented with a 3-week history of dizziness, recurrent near-syncopal episodes and generalized weakness. He was found to have sustained polymorphic ventricular tachycardia in the setting of cardiac melanoma. We draw attention to an unusual presentation of malignant melanoma with cardiac metastasis and discuss both its etiology and treatment options.

Diabetes Care Management In The Cancer Center: Challenging Current Models Of Care To Optimize Outcomes For A Complex Population, Cara Habeck Rn, Cde, Joyce Najarian Msn, Rn, Cde, Gregory R. Harper Md, Phd, Gretchen Perilli Md, Janelle M. Sharma Dnp, Crnp, Melissa Kratz Rn, Msn, Aocn, Patricia Shearburn Rn, Msn, Aocn, Cathy A. Coyne Phd, Mph, Hope Kincaid Mph, Cph, Roya Hamadani Mph

Patient Care Services / Nursing

No abstract provided.

Role Of The Ang-Tie2 Pathway In The Invasive Recurrence Of Gbm Following Anti-Vegf Therapy, Nahir Cortes Santiago

Dissertations and Theses (Open Access)

Strong pre-clinical and clinical data supporting the effectiveness of bevacizumab, a humanized monoclonal anti-VEGF antibody, for the treatment of gliomas led to its accelerated approval for the treatment of patients with recurrent glioma. However, despite strong anti-tumor effects, upon treatment with bevacizumab, patients will invariably recur with a tumor characterized by enhanced invasiveness and resistance to therapy. This study aims to elucidate the mechanisms leading to this enhanced malignancy with the hope of uncovering new potential therapeutic targets for combined treatment. Using tissue sections from U87-derived glioma bearing mice treated with or without aflibercept (another anti-VEGF antibody) we have gathered …

Characterization Of Hcmv-Encoded Chemokine Receptor Us28 Transduced Msu1.1 Human Fibroblast Cells, Danielle R. Vanbeckum

All NMU Master's Theses

Human Cytomegalovirus (HCMV) encodes the G-protein coupled receptor US28. Using a mouse model system, US28 was previously found to be oncomodulatory, increasing proliferation, inducing anchorage independent growth and loss of contact inhibition. Similarly, in the human glioblastoma cell line U373, US28 activated VEGF expression. To determine if US28 is oncomodulatory in normal human cells, we engineered the human fibroblast cell line MSU1.1 to express US28 via lentivirus infection. MSU1.1 cells were transduced with pHAGE-US28-ZsGreen. Fluorescent confocal microscopy was utilized to detect the ZsGreen tag and confirmed the successful transduction of MSU1.1 cells with the US28 vector or empty pHAGE vector. …

Role Of Macrophages In Adaptive Resistance To Anti-Vegf Therapy, Heather Dalton

Dissertations and Theses (Open Access)

Background: The clinical implementation of therapies targeting the VEGF pathway in cancer has been limited by acquired resistance; yet, the mechanisms by which this occurs is unclear. We investigated the role of macrophages in the development of acquired resistance to anti-VEGF antibody (AVA) therapy.

Materials and Methods: We first established a murine ovarian cancer model of resistance to anti-VEGF therapy. Using this model we investigated changes in macrophage infiltration during AVA sensitive and resistant phases. We also investigated the in vivo effects of macrophage depletion at the emergence of anti-VEGF resistance and in upfront combination with AVA therapy. In vitro …

Notch Signaling Inhibited By Ikaros1 In Human T-Cell Acute Lymphoblastic Leukemia, Camille W. Graham

Dissertations and Theses (Open Access)

The highly conserved Notch signaling pathway regulates cell growth, differentiation, survival and apoptosis. In hematopoiesis, Notch signaling drives commitment to the T-cell fate and promotes differentiation, T-cell receptor signaling and immune function. In T-cells, Notch signaling is oncogenic when constitutively active, promoting proliferation and survival while inhibiting differentiation. The majority of patients with T-cell acute lymphoblastic leukemia (TALL) have activating Notch mutations. Similarly, Notch activation is present in more than 75% of murine T-ALL models. In murine T-ALL, loss of Ikaros, a zinc finger transcriptional regulator, leads to disrupted differentiation and also cooperates with activated Notch signaling to promote T-ALL. …