Neoplasms Commons^™

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

Ron - The Con In Colorectal Carcinoma, Shikha Tarang, J. Wang

Journal Articles: Eppley Institute

The recepteur d’origine nantais (RON) is a member of MET family of receptor tyrosine kinase (RTKs), an overexpression of which has been observed in several cancers. The expression of RON gene is required during embryonic development and also plays critical roles in regulating macrophage inflammatory response. In CRC, the overexpression of moderate RON activity contributes to their oncogenic potential by regulating several key processes such as proliferation, motility and resistance to apoptosis. Interestingly, an aberrant RON expression is often associated with the generation of several splice variants with unique transforming activities. The targeting of RON signaling pathway by the use …

A Heuristic Solution Of The Identifiability Problem Of The Age-Period-Cohort Analysis Of Cancer Occurrence: Lung Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

BACKGROUND: The Age-Period-Cohort (APC) analysis is aimed at estimating the following effects on disease incidence: (i) the age of the subject at the time of disease diagnosis; (ii) the time period, when the disease occurred; and (iii) the date of birth of the subject. These effects can help in evaluating the biological events leading to the disease, in estimating the influence of distinct risk factors on disease occurrence, and in the development of new strategies for disease prevention and treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel approach for estimating the APC effects on disease incidence rates in the frame of …

Differential Expression Of Metabolic Genes In Tumor And Stromal Components Of Primary And Metastatic Loci In Pancreatic Adenocarcinoma., Nina V. Chaika, Fang Yu, Vinee Purohit, Kamiya Mehla, Audrey J. Lazenby, Dominick J. Dimaio, Judy M. Anderson, Jen Jen Yeh, Keith R. Johnson, Michael A. Hollingsworth, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways …

Gentamicin Rapidly Inhibits Mitochondrial Metabolism In High-Frequency Cochlear Outer Hair Cells, Heather Jensen Smith, Richard Hallworth, Michael G. Nichols

Journal Articles: Eppley Institute

Aminoglycosides (AG), including gentamicin (GM), are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL) in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs) preferentially succumb to multiple HL pathologies while inner hair cells (IHCs) are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH) fluorescence during acute (1 h) GM treatment …

Examining Cancer-Related Pain And Quality Of Life In Lehigh Valley Home Care Patients, Linda G. Alley Phd, Rn, Hannah D. Paxton Rn, Mph, Michelle D. Flores Bsn, Rn, Carol A. Foltz Phd, Jen Wike Mph, Mba, Vickie Cunningham Bsn, Rn, Jeffrey Etchason Md

Administration & Leadership

No abstract provided.

Deletion Of Rb Accelerates Pancreatic Carcinogenesis By Oncogenic Kras And Impairs Senescence In Pre-Malignant Lesions, Catherine Carrière, A. Jesse Gore, Alixanna M. Norris, Jason R. Gunn, Alison Young, Daniel Longnecker, Murray Korc

Dartmouth Scholarship

Rb1 encodes a cell-cycle regulator that is functionally disrupted in most human cancers. Pancreatic ductal adenocarcinomas (PDACs) have a high frequency of mutations in KRAS and INK4A/CDKN2A that might allow cells to bypass the regulatory actions of retinoblastoma (RB). To determine the role of loss of RB function in PDAC progression, we investigated the effects of Rb disruption during pancreatic malignant transformation initiated by oncogenic Kras.We generated mice with pancreas-specific disruption of Rb, in the absence or presence of oncogenic Kras, to examine the role of RB in pancreatic carcinogenesis.

Self-Reported Exercise And Risk Of Osteoporosis In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Lori J. Mennen-Winchell

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer is stimulated to grow in response to testosterone. Androgen deprivation therapy (ADT) leads to chemical castration and suppression of prostate cancer cell production. Testosterone levels less then 300ng/ml decreases bone mineral density and could result in osteoporosis. Studies have shown that during the first year of ADT, fracture risk, mainly in hips and spine increases about 50%. In men, 40% of hip fractures result in death. Exercise may reduce the risk of osteoporosis and thus contribute to the prevention of hip and other fractures. There is limited data regarding whether exercise is associated with a reduced risk of …

Renal Thrombotic Microangiopathy In Mice With Combined Deletion Of Endocytic Recycling Regulators Ehd3 And Ehd4., Manju George, Mark A. Rainey, Mayumi Naramura, Kirk W. Foster, Melissa S. Holzapfel, Laura L. Willoughby, Guoguang Ying, Rasna M. Goswami, Channabasavaiah B. Gurumurthy, Vimla Band, Simon C. Satchell, Hamid Band

Journal Articles: Eppley Institute

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3(-/-) mice and assessed renal development and pathology. Ehd3(-/-) animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3(-/-) mice and suggested functional compensation, we generated and analyzed Ehd3(-/-); Ehd4(-/-) mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between …

The Roles Of Conserved And Nonconserved Cysteinyl Residues In The Oligomerization And Function Of Mammalian Prestin, Benjamin Currall, Danielle Rossino, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

The creation of several prestin knockout and knockin mouse lines has demonstrated the importance of the intrinsic outer hair cell membrane protein prestin to mammalian hearing. However, the structure of prestin remains largely unknown, with even its major features in dispute. Several studies have suggested that prestin forms homo-oligomers that may be stabilized by disulfide bonds. Our phylogenetic analysis of prestin sequences across chordate classes suggested that the cysteinyl residues could be divided into three groups, depending on the extent of their conservation between prestin orthologs and paralogs or homologs. An alanine scan functional analysis was performed of all nine …

Microrna-183 Family Expression In Hair Cell Development And Requirement Of Micrornas For Hair Cell Maintenance And Survival, Michael D. Weston, Marsha L. Pierce, Heather Jensen Smith, Bernd Fritzsch, Sonia Rocha-Sanchez, Kirk W. Beisel, Garrett A. Soukup

Journal Articles: Eppley Institute

MicroRNAs (miRNAs) post-transcriptionally repress complementary target gene expression and can contribute to cell differentiation. The coordinate expression of miRNA-183 family members (miR-183, miR-96, and miR-182) has been demonstrated in sensory cells of the mouse inner ear and other vertebrate sensory organs. To further examine hair cell miRNA expression in the mouse inner ear, we have analyzed miR-183 family expression in wild type animals and various mutants with defects in neurosensory development. miR-183 family member expression follows neurosensory cell specification, exhibits longitudinal (basal-apical) gradients in maturating cochlear hair cells, and is maintained in sensory neurons and most hair cells into adulthood. …

The Relationship Between The Level Of Support Group Participation And Psychosocial Factors In Prostate Cancer Patients Treated With Proton Therapy, Carol A. L. Davis

Loma Linda University Electronic Theses, Dissertations & Projects

Background. The role of support groups for cancer patients is known to be beneficial in helping people adjust to the disease, and cope with the myriad of effects that cancer has on quality of life. Although many people express interest in attending such support groups, few attend regularly. It is unclear what characteristics distinguish those who use such services from those who do not, especially among proton therapy patients.

Objective. To examine demographic and psychosocial characteristics associated with the Brotherhood of the Balloon (BOB) prostate cancer support group membership, a unique treatment-focused group originating at Loma Linda University Medical Center …

Lung Carcinoma: Its Profile And Changing Trends, Saad Siddiqui, Mohammed Usman Ali, Mahrukh Ayesha Ali, Noreen Shah, Shagufta Nasreen

Section of Pulmonary & Critical Care

BACKGROUND: Lung Carcinoma is the leading causes of morbidity and mortality worldwide with an incidence of 1.3 million cases per year. This study was undertaken to determine prevalence of various histological types of lung carcinoma and to analyse their changing trends with time.

METHODS: This is a retrospective analytical study. A total of 330 cases of lung carcinoma were analysed from 2003 to 2008. Cases from Khyber Pakhtunkhwa and Federally Administered Tribal Area (FATA) were included in this study. Furthermore, only cases of lung carcinoma were considered while other malignancies were excluded.

RESULTS: Squamous Cell carcinoma was found in 42.7% …

Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil

Rowan-Virtua School of Osteopathic Medicine Departmental Research

K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased …

Evaluating The Impact Of The Guatemalan Nursing Program On Staff, Organizational, And Clinical Outcomes, Sara Williamson Day

Theses and Dissertations (ETD)

There is great disparity between the outcome of childhood cancer in developed and developing countries. Nurses, who comprise the largest group of health care professionals globally, are essential to successful treatment. Pediatric oncology education is generally unavailable for nurses in developing countries. This lack of education is likely to contribute to the disparity in survival rates, as undereducated nurses are unable to meet the demands of pediatric cancer care. A second critical problem in developing countries is the workload of the nurse, with a patient nurse ratio reported as high as 30 patients per one nurse.

In 2006, the quality …

Pregnancy Associated Breast Cancer: An Analysis Of Fetal Treatment Risk, Melissa Barnett

The Science Journal of the Lander College of Arts and Sciences

There are several viable treatment options for patients with PABC considered un-harmful to fetal development. Trastusumab, or Herceptin, targets HER2 protein and successfully combats aggressive breast cancer. In standard doses, it appears to be safe to the fetus even when administered during the first trimester. A likely side effect of Herceptin is anhydramnios, which can be monitored for throughout the stages of a pregnancy (Shrim et al. 2008). Anthracyclines, commonly used in chemotherapy, appear to be non-toxic, and have been used to successfully cure PABC patients in their second and third trimester. However, first trimester spontaneous abortions are documented to …

Cyclin D1 Amplification In Tongue And Buccal Mucosa Squamous Cell Carcinoma., Haydar M. Mahdey

Student Works (2010-2019)

Introduction Oral cancer is a significant health problem worldwide with almost 300,000 new cases are diagnosed each year. Despite the numerous studies done, and even with the best treatment option utilized, more than 50% of patients with oral cancer will experience relapse. In search for better options for prognostication, researches are now focusing on the molecular biology of cancer, for instance in search of reliable tumor markers. Among the markers reported in the literatures, Cyclin D1 is actively studied protein. Cyclin D1 regulates the cell cycle progression by forming a complex with different cyclin dependant kinase. Dysregulation of cyclin D1 …

The Neighborhood Cancer Center, Gregory R. Harper Md, Phd, Debbie Salas-Lopez Md, Mph, Keith J. Weinhold Mha, Elliot J. Sussman Md, Mba

Administration & Leadership

No abstract provided.

Inadequate Health Numeracy Affects Cancer Screening Practices In Vulnerable Populations, Sherrine Eid Mph, Dorothy Faulkner Phd

Administration & Leadership

No abstract provided.

A Generalized Beta Model For The Age Distribution Of Cancers: Application To Pancreatic And Kidney Cancer., Tengiz Mdzinarishvili, Michael X. Gleason, Leo Kinarsky, Simon Sherman

Journal Articles: Eppley Institute

The relationships between cancer incidence rates and the age of patients at cancer diagnosis are a quantitative basis for modeling age distributions of cancer. The obtained model parameters are needed to build rigorous statistical and biological models of cancer development. In this work, a new mathematical model, called the Generalized Beta (GB) model is proposed. Confidence intervals for parameters of this model are derived from a regression analysis. The GB model was used to approximate the incidence rates of the first primary, microscopically confirmed cases of pancreatic cancer (PC) and kidney cancer (KC) that served as a test bed for …

Primary Cutaneous B Cell Lymphoma--Leg Type (New Eortc--Who Classification), With Nasal Sinuses Involvement, Asim Jamal Shaikh, Nehal Masood, Aamir Ahsan, Wasim Memon

Department of Radiation Oncology

Primary Cutaneous lymphomas of B cell origin are rare, there remains a controversy in truly classifying these lymphomas and an updated EORTC classification divides them on the basis of their distinct histopthological grounds rather than on the basis of their anatomic location as in WHO classification, while the new WHO- EORTC joint classification maintains some characteristics of both systems, We report an elderly gentleman who primarily had a typical Leg dominant Cutaneous lymphoma of B cell origin uniquely with involvement of nasal Sinusues, bearing the Immunohistochemical staining features of "Cutaneous lymphoma - Leg Type" befitting the new joint WHO-EORTC classification …

Inhibition Of Signal Transducer And Activator Of Transcription 3 Expression By Rna Interference Suppresses Invasion Through Inducing Anoikis In Human Colon Cancer Cells, Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Hua Li

Dartmouth Scholarship

AIM: To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference.

Nitrated Alpha-Synuclein Immunity Accelerates Degeneration Of Nigral Dopaminergic Neurons., Eric J. Benner, Rebecca Banerjee, Ashley D. Reynolds, Simon Sherman, Vladimir M. Pisarev, Vladislav Tsiperson, Craig Nemachek, Pawel Ciborowski, Serge Przedborski, R. Lee Mosley, Howard Gendelman

Journal Articles: Eppley Institute

BACKGROUND: The neuropathology of Parkinson's disease (PD) includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn) enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.

METHODS AND FINDINGS: Nitrotyrosine (NT)-modified alpha-Syn was detected readily in cervical lymph nodes (CLN) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Antigen-presenting cells within the CLN …

Selective Repression Of Retinoic Acid Target Genes By Rip140 During Induced Tumor Cell Differentiation Of Pluripotent Human Embryonal Carcinoma Cells, Kelly C. Heim, Kristina A. White, Dexin Deng, Craig R. Tomlinson, Jason Moore, Sarah Freemantle, Michael Spinella

Dartmouth Scholarship

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification …

Predictors Of Emotional Reactions In Women Treated For Breast Cancer, Erin E. Ramirez

Loma Linda University Electronic Theses, Dissertations & Projects

Breast cancer can be a devastating disease that impacts a woman in all spheres of her life (Ingram, 1989). Previous studies have examined the impact of breast cancer on body satisfaction, as well as the impact on emotional well-being. Studies have also examined the role of the coping style that a woman engages in response to the diagnosis and treatment of breast cancer in the woman's psychological adjustment to the disease. However, to date, no research has introduced and tested a multifaceted model.

The purpose of this study was to develop a model predicting psychological maladjustment in women treated for …

Let-7 Expression Defines Two Differentiation Stages Of Cancer, Scott Shell, Sun-Mi Park, Amir Reza Radjabi, Robert Schickel, Emily Kistner, David Jewell

Dartmouth Scholarship

The early phases of carcinogenesis resemble embryonic development, often involving the reexpression of embryonic mesenchymal genes. The NCI60 panel of human tumor cell lines can genetically be subdivided into two superclusters (SCs) that correspond to CD95 Type I and II cells. SC1 cells are characterized by a mesenchymal and SC2 cells by an epithelial gene signature, suggesting that SC1 cells represent less differentiated, advanced stages of cancer. miRNAs are small 20- to 22-nucleotide-long noncoding RNAs that inhibit gene expression at the posttranscriptional level. By performing miRNA expression analysis on 10 Type I and 10 Type II cells, we have determined …

The Nestin Progenitor Lineage Is The Compartment Of Origin For Pancreatic Intraepithelial Neoplasia, Catherine Carriere, Elliot S. Seeley, Tobias Goetze, Daniel S. Longnecker, Murray Korc

Dartmouth Scholarship

To determine the cell compartment in which initial oncogenic mutations occur in pancreatic ductal adenocarcinoma (PDAC), we generated a mouse model in which endogenous expression of mutated Kras (Kras(G12D)) was initially directed to a population of pancreatic exocrine progenitors characterized by the expression of Nestin. Targeting of oncogenic Kras to such a restricted cell compartment was sufficient for the formation of pancreatic intraepithelial neoplasias (PanINs), putative precursors to PDAC. PanINs appeared with the same grade and frequency as observed when Kras(G12D) was targeted to the whole pancreas by a Pdx1-driven Cre recombinase strategy. Thus, the Nestin cell lineage is highly …

Colon Carcinoma Cells Harboring Pik3ca Mutations Display Resistance To Growth Factor Deprivation Induced Apoptosis., J. Wang, Karen Kuropatwinski, Jennie Hauser, Michael R. Rossi, Yunfei Zhou, Alexis Conway, Julie L.C. Kan, Neil W. Gibson, James K.V. Willson, John K. Cowell, Michael G. Brattain

Journal Articles: Eppley Institute

PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is mutated in a variety of human cancers. We screened the colon cancer cell lines previously established in our laboratory for PIK3CA mutations and found that four of them harbored gain of function mutations. We have now compared a panel of mutant and wild-type cell lines for cell proliferation and survival in response to stress. There was little difference in PI3K activity between mutant PIK3CA-bearing cells (mutant cells) and wild-type PIK3CA-bearing cells (wild-type cells) under optimal growth conditions. However, the mutant cells showed constitutive PI3K activity during growth factor deprivation …

Long-Distance Three-Color Neuronal Tracing In Fixed Tissue Using Neurovue Dyes, Heather Jensen Smith, Brian Gray, Katharine Muirhead, Betsy Ohlsson-Wilhelm, Bernd Fritzsch

Journal Articles: Eppley Institute

Dissecting development of neuronal connections is critical for understanding neuronal function in both normal and diseased states. Charting the development of the multitude of connections is a monumental task, since a given neuron typically receives hundreds of convergent inputs from other neurons and provides divergent outputs for hundreds of other neurons. Although progress is being made utilizing various mutants and/or genetic constructs expressing fluorescent proteins like GFP, substantial work remains before a database documenting the development and final location of the neuronal pathways in an adult animal is completed. The vast majority of developing neurons cannot be specifically labeled with …

Lateral Wall Protein Content Mediates Alterations In Cochlear Outer Hair Cell Mechanics Before And After Hearing Onset, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

Specialized outer hair cells (OHCs) housed within the mammalian cochlea exhibit active, nonlinear, mechanical responses to auditory stimulation termed electromotility. The extraordinary frequency resolution capacity of the cochlea requires an exquisitely equilibrated mechanical system of sensory and supporting cells. OHC electromotile length change, stiffness, and force generation are responsible for a 100-fold increase in hearing sensitivity by augmenting vibrational input to non-motile sensory inner hair cells. Characterization of OHC mechanics is crucial for understanding and ultimately preventing permanent functional deficits due to overstimulation or as a consequence of various cochlear pathologies. The OHCs' major structural assembly is a highly-specialized lateral …