Diseases Commons^™

Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Only 30% of patients diagnosed with pancreatic cancer survive one year post-diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

Impact Of Tumour Epithelial Subtype On Circulating Micrornas In Breast Cancer Patients, Peadar S. Waters, Roisin M. Dwyer, Cathy Brougham, Claire L. Glynn, Deidre Wall, Peter Hyland, Maria Duignan, Mark Mcloughlin, John Newell, Michael J. Kerin

Forensic Science Publications

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and …

Molecular Pap Biomarkers For Cervical Cancer Risk Assessment In Thinprep® Clinical Specimens, Jennifer Taylor

Graduate School of Biomedical Sciences Theses and Dissertations

Approximately 500,000 patients are diagnosed with cervical cancer worldwide each year, thus making it the second most common cause of cancer-related deaths in women. Persistent high-risk human papillomavirus (HR-HPV) infections induce cervical dysplasia by increasing the expression of two viral oncogenes, E6 and E7. Utilization of the Papanicolaous smear test (Pap test) has contributed to a decrease in morbidity and mortality of cervical cancer; however, subjective analysis of cell morphology with a limited amount of cells has led to a substantial rate of false positive and false negative diagnoses. A more objective and sensitive diagnostic tool for the detection of …

Natural History Of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer In Men With Favorable Prognostic Indicators, Andrew Renshaw

All Publications

No abstract provided.

The Relationship Between Area Poverty Rate And Site-Specific Cancer Incidence In The United States, Francis P. Boscoe, Christopher J. Johnson, Recinda L. Sherman, David G. Stinchcomb, Ge Lin, Kevin A. Henry

Epidemiology & Biostatistics Faculty Scholarship

BACKGROUND

The relationship between socioeconomic status and cancer incidence in the United States has not traditionally been a focus of population-based cancer surveillance systems.

METHODS

Nearly 3 million tumors diagnosed between 2005 and 2009 from 16 states plus Los Angeles were assigned into 1 of 4 groupings based on the poverty rate of the residential census tract at time of diagnosis. The sex-specific risk ratio of the highest-to-lowest poverty category was measured using Poisson regression, adjusting for age and race, for 39 cancer sites.

RESULTS

For all sites combined, there was a negligible association between cancer incidence and poverty; however, …

Prc2 Is Recurrently Inactivated Through Eed Or Suz12 Loss In Malignant Peripheral Nerve Sheath Tumors, W. Lee, S. Teckie, T. Wiesner, A. Viale, S. Singer, D. Zheng, M. F. Berger, Y. Chen, C. R. Antonescu, P. Chi, +11 Additional Authors

Journal Articles

Malignant peripheral nerve sheath tumors (MPNSTs) represent a group of highly aggressive soft-tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1 associated) or after radiotherapy. Using comprehensive genomic approaches, we identified loss-of-function somatic alterations of the Polycomb repressive complex 2 (PRC2) components (EED or SUZ12) in 92% of sporadic, 70% of NF1-associated and 90% of radiotherapy-associated MPNSTs. MPNSTs with PRC2 loss showed complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3) and aberrant transcriptional activation of multiple PRC2-repressed homeobox master regulators and their regulated developmental pathways. Introduction of the lost PRC2 component in a …

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …

Transcriptional Diversity Of Long-Term Glioblastoma Survivors, N. K. Gerber, A. Goenka, S. Turcan, M. Reyngold, V. Makarov, K. Kannan, K. Beal, C. W. Brennan, J. T. Huse, T. A. Chan, +3 Additional Authors

Journal Articles

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia …

Defining Internal Target Volume Using Positron Emission Tomography For Radiation Therapy Planning Of Moving Lung Tumors, A. C. Riegel, M. K. Bucci, O. R. Mawlawi, M. Ahmad, D. Luo, A. Chandler, T. S. Pan

Journal Articles

Substantial disagreement exists over appropriate PET segmentation techniques for non-small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source-to-background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of …

Weighing The Risks And Benefits Of Radiation Exposure And Diagnostic X-Rays In Children, Leah Costello

Physician Assistant Scholarly Project Posters

The number of X-rays, specifically CT scans, performed on patients in the United States is increasing exponentially every year. Children are at most risk for long term damage from this increase in radiation exposure. This study explores how much risk children are being exposed to and how we can, as practitioners, make informed decisions about when or when not to order CT scans. The purpose of this paper is to provide practitioners the information needed to help patients decide if the long-term risks of cancer from medical radiation outweigh the potential benefit of diagnostic or therapeutic radiation. The review of …

The Role Of Mammalian Cyclin C In Stress Response And Thyroid Disease Progression, Kun Wang

Graduate School of Biomedical Sciences Theses and Dissertations

The cellular response to stress involves changes in gene expression programs as well as the remodeling of subcellular organelles including the mitochondria. Important for this study, the mitochondria undergo extensive fragmentation when the cell is exposed to a variety of stressors. The cyclin C-Cdk8 kinase is a highly conserved transcription factor that associates with the RNA polymerase II holoenzyme. Using cyclin C knockout (CCNC^-/-) mouse embryonic fibroblast (MEF) cells, I revealed that cyclin C is required for the extensive mitochondrial fragmentation following treatment with pro-oxidants or the anti-cancer drug cisplatin. However, Cdk8 is not required for this process …

Parp Inhibition: A Method Of Treating And Preventing Certain Cancers, Chana Tropper

The Science Journal of the Lander College of Arts and Sciences

Breast cancer is one of the largest causes of cancer related deaths in women. Less than 5% of breast cancer cases are genetically inherited and most often develop after menopause. The BRCA gene mutation is a genetic inheritance which increases ones chances of developing breast cancer at a young age tenfold. Recent research has proposed a method of treatment in genetically inherited breast cancers by taking advantage of the impaired DNA repair pathway caused by the BRCA mutation. The combination of a BRCA mutation, which leads to deficient double strand DNA repair, and PARP inhibition, which leads to deficient single …

Muc1 Regulates Cyclin D1 Gene Expression Through P120 Catenin And Β-Catenin, X. Liu, Thomas C. Caffrey, M. M. Steele, Ashley M. Mohr, Pankaj K. Singh, Prakash Radhakrishnan, David L. Kelly, Y. Wen, Michael A. Hollingsworth

Journal Articles: Eppley Institute

MUC1 interacts with β-catenin and p120 catenin to modulate WNT signaling. We investigated the effect of overexpressing MUC1 on the regulation of cyclin D1, a downstream target for the WNT/β-catenin signaling pathway, in two human pancreatic cancer cell lines, Panc-1 and S2-013. We observed a significant enhancement in the activation of cyclin D1 promoter-reporter activity in poorly differentiated Panc1.MUC1F cells that overexpress recombinant MUC1 relative to Panc-1.NEO cells, which express very low levels of endogenous MUC1. In stark contrast, cyclin D1 promoter activity was not affected in moderately differentiated S2-013.MUC1F cells that overexpressed recombinant MUC1 relative to S2-013.NEO cells that …

Correlation Of Ischemia-Modified Albumin With Sofa And Apache Ii Scores In Preoperative Patients With Colorectal Cancer, Masaaki Katoh, Kazuhiko Kotani, Alejandro Gugliucci, Hisanaga Horie, Russell Caccavello, Mamoru Takeuchi

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Purpose. Critical illnesses are assessed according to the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) II. Circulating ischemia-modified albumin (IMA) is a biomarker generated under ischemic and oxidative conditions and may reflect disease severity in preoperative patients. This study investigated the correlations of IMA with SOFA and APACHE II scores in inpatients admitted for colorectal surgery. Methods.We examined 27 patients with advanced colorectal cancers (mean age 69 years, men/women = 15/12). Correlations between SOFA and APACHE II scores in addition to preoperative serum IMA and C-reactive protein (CRP) levels were analyzed. Results …

Immunotherapy As A Treatment Option For Patients With Pancreatic Cancer, Yehuda Lehrfield

The Science Journal of the Lander College of Arts and Sciences

Pancreatic cancer is one of the worst forms of cancer that can develop in an individual. Traditionally, chemotherapy is administered but it has very limited success. Using the immune system to treat the cancer is very enticing and many studies have been conducted to attempt to harness the body’s own mechanisms to defeat the cancer. It seems that in order to properly treat the tumor a two pronged approach must be used. First, the immune system must be stimulated to react to the tumor and attack it. A possible cytokine that can be utilized is interferon alpha, which could result …

Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook

PCOM Biomedical Studies Student Scholarship

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh

Faculty Publications

Background

Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration.

Methods

To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHY_TG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to …

Is Massage Therapy An Effective Treatment For Improving Sleep Quality In Women Age 50-80 Diagnosed With Cancer?, Alexander M. Chase

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not massage therapy is an effective treatment in improving sleep quality among women age 50-80 diagnosed with cancer.

STUDY DESIGN: Review of two English language randomized control trials published in 2004 and 2011 and one English language quasiexperimental pretest-posttest comparison study publishEd in 2002.

DATA SOURCES: Data sources were articles published in peer reviewed journals found using PubMed and EBSCOhost.

OUTCOMES MEASURED: Sleep quality was measured using the Verran and Snyder-Halpem Sleep Scale and the Richards-Campbell Sleep Questionnaire.

RESULTS: Soden et al …

Is Bevacizumab (Avastin) Safe And Effective As Adjuvant Chemotherapy For Adult Patients With Stage Iiib Or Iv Non-Small Cell Lung Carcinoma (Nsclc)?, Ashley R. De Kleine

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not bevacizumab (avastin) is safe and effective as adjuvant chemotherapy for adult patients with stage IIIb or IV non-small cell lung carcinoma (NSCLC).

STUDY DESIGN: Review of three randomized controlled trials (RCT) published in 2006, 2009, and 2011, all English language.

DATA SOURCES: Two randomized, double-blind, controlled clinical trials comparing bevacizumab to placebo as adjunctive chemotherapy, and one RCT comparing bevacizumab as adjunctive chemotherapy versus the use of no adjunctive chemotherapy. All articles were found using PubMed, Medline, and OVID.

OUTCOMES MEASURED: Overall …

Is Music Therapy Effective In Improving Emotional Health In Pediatric Cancer Patients?, Elizabeth F. Matesa

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this evidence based medicine review is to determine whether music therapy is effective in improving emotional health in pediatric cancer patients

STUDY DESIGN: Two randomized controlled trials and a prospective cohort study were reviewed and selected based on their relevance to the clinical question and their inclusion of patient oriented outcomes (POEMS).

DATA SOURCES: Each study was obtained by searching PubMed database.

OUTCOMES MEASURED: The outcomes measured included pain scores measured using a NRS pain scoring scale, anxiety scores were measured using the Spielberger State-Trait Anxiety Inventory (STAI)and visual analog score …

Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn

Theses and Dissertations

Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of …

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.

A Comparison Of Prostatic Acid Phosphatase With Testosterone And Prostate Specific Antigen For The Serodiagnosis Of Prostate Cancer In Adult Males, Hannah R. Rice

Honors Theses

Cancer is a hyperplastic cellular malignancy that affected 1,436,000 people (newly diagnosed cases) in the United States last year. The top three most frequent forms of cancer were lung, prostate, and breast. Oncogenesis is associated with both genetic predisposition and environmental onslaught, with a mixture of the two being required for the malignancy to progress. Tumor markers, circulating serum factors, are used in the diagnosis of cancer. Prostate cancer is one of the most prevalent forms of this malignancy, affecting 230,110 men in 2004 alone. Diagnosis of prostate cancer is currently performed using results of an assay for prostate specific …

Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu

Loma Linda University Electronic Theses, Dissertations & Projects

Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. …

Development And Characterization Of A Recombinant Vesicular Stomatitis Virus (Rvsv) For The Treatment Of Glioblastoma, Erika A. Dillard

Theses and Dissertations (ETD)

Background: Over the past 30 years, little has changed in the treatment modalities and prognosis of patients suffering from Glioblastoma multiforme (GBM), the most common and by far the most devastating adult primary malignant brain tumor. Conventional therapies provide only a marginal increase in survival of GBM patients, post-diagnosis. Therefore, more novel means of treating GBM are needed to increase long-term survival and quality of life for those affected. Replication competent oncolytic viruses (OVs) have recently emerged as a possible option for treatment of high-grade gliomas. Particularly, recombinant vesicular stomatitis virus (rVSV), an enveloped, negative strand RNA virus, has shown …

Nkg2d Ligands In Cancer, Neha Das Gupta

Theses and Dissertations (ETD)

NK cell transplantation has been increasingly used to treat cancers that are resistant to chemotherapy. However, not all cancers are susceptible to NK cell killing. The prevalence and mechanisms of NK cell resistance have not been well elucidated. Because NKG2D is a major activating receptor on NK cells, we sought to test the hypothesis that NKG2D is the primary pathway in tumor cell recognition. Herein, we comprehensively assessed 20 cancer cell lines representing a broad array of cancer types. In line with our primary hypothesis, no cancer cell lines that expressed low levels of NKG2D ligands were susceptible to NK …

Tetraspanin Cd9: Contributions To Cancer Cell And Vascular Cell Phenotypes From The Sixth Man, Michael James Herr Ii

Theses and Dissertations (ETD)

Cancer and vascular disease are the two most predominant causes of mortality in the United States. Potential regulatory mechanisms for these two diseases have consumed research interests. Tetraspanins are cell surface proteins that organize the cell membrane. Cellular membrane organization is a prerequisite for cellular signaling to occur. Deregulation of cellular signaling often precedes the formation of cancer or vascular disease phenotypes. This insinuates the necessity to understand how tetraspanins contribute to membrane organization and subsequent downstream signaling. This work examines tetraspanin CD9 contributions in a model of cancer cell invasion and vascular cell contraction. The findings presented here demonstrate …