Medicine and Health Sciences Commons^™

A Meta-Analysis Of Array-Cgh Studies Implicates Antiviral Immunity Pathways In The Development Of Hepatocellular Carcinoma., Xu Guo, Yanna Ba, Xi Ma, Jiaze An, Yukui Shang, Qichao Huang, Hushan Yang, Zhinan Chen, Jinliang Xing

Kimmel Cancer Center Faculty Papers

BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.

METHODS: In present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples.

RESULTS: Eighty …

Risk Factors Of Gallbladder Cancer In Karachi-A Case-Control Study, A. Rehman Alvi, Nadeem Ahmed Siddiqui, Hasnain Zafar

Department of Surgery

Background:Gallbladder carcinoma (GC) is a relatively rare malignancy worldwide but is the second commonest gastrointestinal cancer in Pakistani women. Gallstones have a positive association with GC but other factors also influence in causation.

Methods:

This is a retrospective case control study over a period of 19 years. The cases (Group A) were Patients with histopathological proven carcinoma gallbladder (N = 60) and controls were Patients with cholelithiasis but no carcinoma gallbladder on histopathology (N = 120). Multivariate regression analysis was done to calculate the odds ratio, 95% confidence interval and P-Value. A positive relationship was found between size of …

Interferon Alpha For Chronic Hepatitis D, Zaigham Abbas, Muhammad Arsalan Khan, Mohammad Salih, Wasim Jafri

Department of Medicine

Background:

Hepatitis D virus is a small defective RNA virus that requires the presence of hepatitis B virus infection to infect a person. Hepatitis D is a difficult-to-treat infection. Several clinical trials have been published on the efficacy of interferon alpha for hepatitis D virus (HDV) infection. However, there are few randomised trials evaluating the effects of interferon alpha, and it is difficult to judge any benefit of this intervention from the individual trials.

Objectives:

To evaluate the beneficial and harmful effects of interferon alpha for Patients with chronic hepatitis D.

Search methods:

We identified relevant for the review randomised …

Patterns Of Information Behavior And Prostate Cancer Knowledge Among African-American Men, Levi Ross, Tyra Dark, Heather Orom, Willie Underwood Iii, Charkarra T. Anderson-Lewis, Jarrett Johnson, Deborah O. Erwin

Faculty Publications

The purposes of this study are to explore cancer information acquisition patterns among African-American men and to evaluate relationships between information acquisition patterns and prostate cancer prevention and control knowledge. A random sample of 268 men participated in a statewide interviewer-administered, telephone survey. Men classified as non-seekers, non-medical source seekers, and medical source seekers of prostate cancer information differed on household income, level of education, and beliefs about personal risk for developing prostate cancer. Results from multiple regression analysis indicated that age, education, and information-seeking status were associated with overall levels of prostate cancer knowledge. Results from logistic regression analyses …

Contribution Of Ectodomain Mutations In Epidermal Growth Factor Receptor To Signaling In Glioblastoma Multiforme, Marta L. Rojas

Dissertations & Theses (Open Access)

CONTRIBUTION OF ECTODOMAIN MUTATIONS IN EPIDERMAL GROWTH FACTOR RECEPTOR TO SIGNALING IN GLIOBLASTOMA MULTIFORME

Publication No._________

Marta Rojas, M.S.

Supervisory Professor: Oliver Bögler, Ph.D.

The Cancer Genome Atlas (TCGA) has conducted a comprehensive analysis of a large tumor cohort and has cataloged genetic alterations involving primary sequence variations and copy number aberrations of genes involved in key signaling pathways in glioblastoma (GBM). This dataset revealed missense ectodomain point mutations in epidermal growth factor receptor (EGFR), but the biological and clinical significance of these mutations is not well defined in the context of gliomas.

In our study, we focused on understanding …

Novel Amino Acid Transporter-Targeted Radiotracers For Breast Cancer Imaging, Fanlin Kong

Dissertations & Theses (Open Access)

Breast cancer is the most common malignancy among women in the world. Its 5-year survival rate ranges from 23.4% in patients with stage IV to 98% in stage I disease, highlighting the importance of early detection and diagnosis. ¹⁸F-2-Fluoro-2-deoxy-glucose (¹⁸F-FDG), using positron emission tomography (PET), is the most common functional imaging tool for breast cancer diagnosis currently. Unfortunately, ¹⁸F-FDG-PET has several limitations such as poorly differentiating tumor tissues from inflammatory and normal brain tissues. Therefore, ¹⁸F-labeled amino acid-based radiotracers have been reported as an alternative, which is based on the fact that tumor cells uptake …

Adaptive Intensity Modulated Radiation Therapy Planning Optimization With Changing Tumor Geometry And Biology Enforcing Both Cumulative And Fraction Size Dose Constraints, Behlul Saka

Graduate Theses and Dissertations

Intensity Modulated Radiation Therapy (IMRT) is a modern technique of delivering radiation treatments to cancer patients. In IMRT technology, intensities must be chosen for the many small unit grids into which the beams are divided to produce a desired distribution of dose at points throughout the body with the goal of maximizing dose delivered to the tumor while sparing healthy tissues from excessive radiation and keeping dose homogeneous across the tumor. Although IMRT plans are optimized as a single overall treatment plan, they are delivered over 30-50 treatment sessions (fractions) and both cumulative and per-fraction dose constraints apply. The extended …

Optimizing Heart Dose Reduction For Deep Inspiration Left Breast Radiotherapy, Ronald James Harder

UNLV Theses, Dissertations, Professional Papers, and Capstones

Multiple studies have shown that an increased risk of late injury cardiac abnormalities including congestive heart failure (CHF), ischemia, and coronary artery disease (CAD) can be associated with common left breast radiation therapy (RT) techniques. Many radiation therapy clinics have adopted the Deep Inspiration Breath Hold (DIBH) technique for the treatment of the left breast with external beam therapy based on studies showing a decrease in the dose received by the heart. A common technology used to monitor inhalation during DIBH is the Real-Time Position Management (RPM) system (Varian Medical Systems, Palo Alto, CA). This study analyzes if there is …

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …

Optical Guidance System Vs. Cbct For Phantom And Patient Setup, L. Fu, H. Perera, H. Liu, Y. Xiao, Y. Yu

Hua Kun Liu

Purpose: To quantify the discrepancy between Varian optical guidance (OG) frameless localization system and Varian Trilogy on board imaging (OBI) system for setting up phantom and SRS patient. American Association of Physicists in Medicine (AAPM) 52nd Annual Meeting July 18-22, Philadelphia, PA

A Procedure For Standardizing Mlc Quality Assurance For Elekta Linac, K. Yan, M. Studenski, H. Liu, I. Buzurovic, Y. Cui, L. Shabason, A. Harrison, Y. Yu, M. Hossain, Y. Xiao

Hua Kun Liu

Purpose: As specified in TG142, MLC position accuracy needs to be tested on weekly/monthly basis, with 1mm tolerance. This study focuses on developing techniques, hardware and software tools for implementation of MLC QA tests for Elekta Linacs. American Association of Physicists in Medicine (AAPM) 52nd Annual Meeting July 18-22, Philadelphia, PA

Implications Of Observation-Fact Modifiers To I2b2 Ontologies, Jack W. London, Devjani Chatterjee

Kimmel Cancer Center Faculty Papers

Biomedical translational research can be facilitated by integrating clinical and research data. In particular, study cohort identification and hypothesis generation is enabled by the mining of integrated clinical observations and research resources. The "informatics for integrating biology and the bedside, " or i2b2, framework is widely used for this biomedical data mining. The i2b2 "star schema" data model using entity-attribute-value (EA V) formatted concepts is a very efficient strategy for querying large amounts of data. However, until the most recent i2b2 release, the utility of the platform was somewhat constrained by the limitations on being able to express "facts about …

Patient-Provider Communication Data: Linking Process And Outcomes In Oncology Care, Lisa Kennedy Sheldon, Fangxin Hong, Donna L. Berry

Nursing Faculty Publication Series

Overview: Patient–provider communication is vital to quality patient care in oncology settings and impacts health outcomes. Newer communication datasets contain patient symptom reports, real-time audiofiles of visits, coded communication data, and visit outcomes. The purpose of this paper is to: (1) review the complex communication processes during patient–provider interaction during oncology care; (2) describe methods of gathering and coding communication data; (3) suggest logical approaches to analyses; and (4) describe one new dataset that allows linking of patient symptoms and communication processes with visit outcomes. Challenges: Patient–provider communication research is complex due to numerous issues, including human subjects’ concerns, methods …

What Should Oncology Nurses Know When Caring For Veterans?, Elizabeth A. Delaney

Nursing Faculty Publications

No abstract provided.

Oncology, Volume 56, Number 11-12, November - December 2011, Sarah Bronson, Zach-Bryan Bogannan-Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Transoral Laser Microsurgery for Laryngeal and Oropharyngeal Tumors: A minimally invasive surgery for treating cancers of the larynx and oropharynx has cute rates similar to those of open surgery and radiation therapy in selected patients.
• Exploring Causes of and Treatments for Neuropathy in Cancer Patients: Among the most troubling side effects of cancer treatment in some patient is chronic chemotherapy neuropathy syndrome, in which tingling, numbness, and pain in the hands and feet persist long after the completion of treatment
• Prostate Cancer Screening: Patient should understand the purpose and limitations of the prostate-specific antigen test
• HOUSE CALL: Smoking Cessation: Medications …

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Proliferating Cell Nuclear Antigen Is Required For Loading Of The Smcx/Kmd5c Histone Demethylase Onto Chromatin., Zhihui Liang, Marc Diamond, Johanna A Smith, Matthias Schnell, René Daniel

Department of Medicine Faculty Papers

UNLABELLED: ABSTRACT:

BACKGROUND: Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking.

RESULTS: In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction. We identified a PCNA-interaction protein motif (PIP box) in the …

New Insights Into The Androgen-Targeted Therapies And Epigenetic Therapies In Prostate Cancer., Abhijit M Godbole, Vincent C O Njar

Kimmel Cancer Center Faculty Papers

Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR), a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC). Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling …

Deregulation Of Micrornas By Hiv-1 Vpr Protein Leads To The Development Of Neurocognitive Disorders, Ruma Mukerjee, J Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya

School of Medicine Faculty Publications

Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic …

Therapeutic Efficacy And Safety Of Paclitaxel/Lonidamine Loaded Egfr-Targeted Nanoparticles For The Treatment Of Multi-Drug Resistant Cancer, Lara S. Jabr-Milane, Zhenfeng Duan, Mansoor M. Amiji

Mansoor M. Amiji

The treatment of multi-drug resistant (MDR) cancer is a clinical challenge. Many MDR cells over-express epidermal growth factor receptor (EGFR). We exploit this expression through the development of EGFR-targeted, polymer blend nanocarriers for the treatment of MDR cancer using paclitaxel (a common chemotherapeutic agent) and lonidamine (an experimental drug; mitochondrial hexokinase 2 inhibitor). An orthotopic model of MDR human breast cancer was developed in nude mice and used to evaluate the safety and efficacy of nanoparticle treatment. The efficacy parameters included tumor volume measurements from day 0 through 28 days post-treatment, terminal tumor weight measurements, tumor density and morphology assessment …

Oncology, Volume 56, Number 10, October 2011, Bryan Tutt, Sunni Hosemann

OncoLog MD Anderson's Report to Physicians (All issues)

• Treating Cancer in Pregnant Patients: Pregnancy is usually a joyous, hopeful time; a cancer diagnosis can be devastating. When pregnancy and cancer occur together, they present special challenges for patients and physicians. Fortunately, these challenges often can be overcome by a multidisciplinary approach to treatment
• Compass: Non-Small Cell Lung Cancer: Stage IIIA-Many factors affect treatment sequences
• HOUSE CALL: Understanding Cancer Risk and Risk Factors: Your risk factors might affect your need for cancer screening

Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina

Kimmel Cancer Center Faculty Papers

BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to …

Multi-Functional Nanocarriers To Overcome Tumor Drug Resistance, Lara S. Jabr-Milane, Lilian E. Van Vlerkin, Sunita Yadav, Mansoor M. Amiji

Mansoor M. Amiji

The development of resistance to variety of chemotherapeutic agents is one of the major challenges in effective cancer treatment. Tumor cells are able to generate a multi-drug resistance (MDR) phenotype due to microenvironmental selection pressures. This review addresses the use of nanotechnology-based delivery systems to overcome MDR in solid tumors. Our own work along with evidence from the literature illustrates the development of various types of engineered nanocarriers specifically designed to enhance tumor-targeted delivery through passive and active targeting strategies. Additionally, multi-functional nanocarriers are developed to enhance drug delivery and overcome MDR by either simultaneous or sequential delivery of resistance …

Pipkiγ Regulates Focal Adhesion Dynamics And Colon Cancer Cell Invasion, Zhaofei Wu, Xiang Li, Manjula Sunkara, Heather Spearman, Andrew J. Morris, Cai Huang

Markey Cancer Center Faculty Publications

Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type Iγ (PIPKIγ) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKIγ promoted focal adhesion formation, whereas cells expressing either PIPKIγ^K188,200R or PIPKIγ^D316K, two kinase-dead mutants, had much fewer focal adhesions than those expressing WT PIPKIγ in CHO-K1 cells and HCT116 colon cancer cells. Furthermore, …

Mechanisms Of Resistance To Raf Inhibitors In Melanoma., A E Aplin, Fred M Kaplan, Yongping Shao

Department of Cancer Biology Faculty Papers

The recent RAF inhibitor trial with PLX4032/RG7204 in late-stage mutant B-RAF melanoma patients has been lauded as a success story for personalized cancer therapy since short-term clinical responses were observed in the majority of patients. However, initial responses were followed by subsequent tumor re-growth, and a subset of patients showed intrinsic resistance. Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors.

Oncology, Volume 56, Number 09, September 2011, Joe Munch, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues)

• Novel Agents for Castrate-Resistant Prostate Cancer Include Potent Androgen Blockers and Immunotherapies: Despite progress in screening and therapy, prostate cancer continues to be a leading cause of cancer death among men worldwide
• New Targeted Therapy Offers Hope in Relapsed Hodgkin and Anaplastic large-Cell Lymphoma: The U.S. Food and Drug Administration (FDA) has approved the first new drug for Hodgkin Lymphoma since 1977
• HOUSE CALL: Colorectal Cancer Screening: Risk factors determine who should be screened and how often
• IN BRIEF: Everolimus may Overcome Trastuzumab Resistance in HER2-Positive Breast Cancer Patients

Critical Role Of Pi3k/Akt/Gsk3Β In Motoneuron Specification From Human Neural Stem Cells In Response To Fgf2 And Egf, Luis Ojeda, Junling Gao, Kristopher G. Hooten, Enyin Wang, Jason R. Thonhoff, Tiffany J. Dunn, Tianyan Gao, Ping Wu

Markey Cancer Center Faculty Publications

Fibroblast growth factor (FGF) and epidermal growth factor (EGF) are critical for the development of the nervous system. We previously discovered that FGF2 and EGF had opposite effects on motor neuron differentiation from human fetal neural stem cells (hNSCs), but the underlying mechanisms remain unclear. Here, we show that FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen synthase kinase 3 beta (GSK3β) activation. High levels of phosphatidylinositol 3-kinase (PI3K)/Akt activation accompanied with GSK3β inactivation result in reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by chemical inhibitors or RNA interference or overexpression of …

Impact Of Age On Outcome After Colorectal Cancer Surgery In The Elderly - A Developing Country Perspective, M. R. Khan, Hassaan Bari, Syed Nabeel Zafar, Syed Ahsan Raza

Department of Surgery

Background:Colorectal cancer (CRC) is a major source of morbidity and mortality in the elderly population and surgery is often the only definitive management option. The suitability of surgical candidates based on age alone has traditionally been a source of controversy. Surgical resection may be considered detrimental in the elderly solely on the basis of advanced age. Based on recent evidence suggesting that age alone is not a predictor of outcomes, Western societies are increasingly performing definitive procedures on the elderly. Such evidence is not available from our region. We aimed to determine whether age has an independent effect on …

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

Strategies For Reducing The Impact Of Tumour Motion During Helical Tomotherapy, Bryan Kim

Electronic Thesis and Dissertation Repository

Tumour motion presents a significant limitation for effective radiotherapy of lung cancer, and more specifically for helical tomotherapy. The simultaneous and continuous movements of tomotherapy subsystems (gantry, couch, and binary multi-leaf collimator) can lead to inaccurate dose delivery, when combined with tumour motion. In this thesis, we have investigated the impact of tumour motion and strategies to reduce the resulting dose discrepancies for helical tomotherapy, through computer simulations and film measurements performed in a dynamic body phantom. Three distinctively different types of dose discrepancies have been isolated: dose rounding, dose rippling, and the intensity-modulated radiation therapy (IMRT) asynchronization effect. Each …