Medical Specialties Commons^™

Ron Knockdown And Ron Monoclonal Antibody Imc-Ron8 Sensitize Pancreatic Cancer To Histone Deacetylase Inhibitors (Hdaci)., Yi Zou, Gillian M. Howell, Lisa E. Humphrey, J. Wang, Michael G. Brattain

Journal Articles: Eppley Institute

Recepteur d'origine nantais (Ron) is overexpressed in a panel of pancreatic cancer cells and tissue samples from pancreatic cancer patients. Ron can be activated by its ligand macrophage stimulating protein (MSP), thereby activating oncogenic signaling pathways. Crosstalk between Ron and EGFR, c-Met, or IGF-1R may provide a mechanism underlying drug resistance. Thus, targeting Ron may represent a novel therapeutic strategy. IMC-RON8 is the first Ron monoclonal antibody (mAb) entering clinical trial for targeting Ron overexpression. Our studies show IMC-RON8 downmodulated Ron expression in pancreatic cancer cells and significantly blocked MSP-stimulated Ron activation, downstream Akt and ERK phosphorylation, and survivin mRNA …

Metaphor Use In Interpersonal Communication Of Body Perception In The Context Of Breast Cancer, Jennifer Mary Fillion

Dissertations and Theses

Female breast cancer patients are often confused, frustrated, and devastated by changes occurring in their bodies and the treatment process. Many women express frustration and concern with the inability to know what the next phases of their life will bring. Previous research also states that many women struggle to communicate with others about treatment as well as side effects. This research examined how woman are use metaphors to describe their experience with breast cancer, specifically throughout the treatment period related to body image struggles. I qualitatively conducted interviews with women who were either currently in treatment or just finishing. My …

Intratumoral Chemotherapy For Lung Cancer: Re-Challenge Current Targeted Therapies, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Kaid Darwiche, Thomas Vogl, Eugene P. Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Francis J. Turner, Patrick Le Pivert, Dionysios Spyratos, Konstantinos Zarogoulidis, Seyhan I. Celikoglu, Firuz Celikoglu, Johannes Brachmann

Internal Medicine Faculty Publications

Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based …

Population Cancer Risks Associated With Coal Mining: A Systematic Review, Wiley D. Jenkins, W. Jay Christian, Georgia Mueller, K. Thomas Robbins

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Coal is produced across 25 states and provides 42% of US energy. With production expected to increase 7.6% by 2035, proximate populations remain at risk of exposure to carcinogenic coal products such as silica dust and organic compounds. It is unclear if population exposure is associated with increased risk, or even which cancers have been studied in this regard.

METHODS: We performed a systematic review of English-language manuscripts published since 1980 to determine if coal mining exposure was associated with increased cancer risk (incidence and mortality).

RESULTS: Of 34 studies identified, 27 studied coal mining as an occupational exposure …

Effect Of Variable Dose Rate On Biologically Effective Dose, Vadim Y. Kuperman, Gregory S. Spradlin

Publications

Purpose: to investigate the effect of variable dose rate on biologically effective dose ( BED ).

Materials and methods: by using the linear-quadratic (LQ) model with bi-exponential repair, we analytically determine the time-dependent dose rate R ~ which minimizes the effective protraction factor ( eff G ) and BEDunder the condition of fixed fraction time and dose per fraction.  Because normal tissue complication probability ( NTCP) monotonically decreases with decreasingBED , the dose rate R ~ also minimizes NTCP.

Results: the dependences of Geff, BED, and NTCP on fraction time were determined for different radiobiological parameters and two different …

Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina

Kimmel Cancer Center Faculty Papers

No abstract provided.

Giant Cell Tumour Of The Sacrum: Function-Preserving Surgery With Extended Curettage And Ilio-Lumbar Fusion, Riaz Hussain Lakhdawala, Tashfeen Ahmad, Ather Enam

Section of Orthopaedic Surgery

Giant cell tumours of the sacrum pose a unique therapeutic challenge due to the inaccessibility of the tumour, significant intra-operative blood loss from extensive vascularity, high rate of local recurrence with conservative surgery, and loss of neurological function and mechanical instability with en-bloc excision. We present a case where successful outcome was achieved by tailoring treatment in consideration of the above issues. A 28 year old male diagnosed on biopsy to have giant cell tumour of the sacrum presented to us with low-back pain, left-sided S1 radiculopathy, ankle weakness and urinary incontinence. MRI showed a tumour involving the S1 and …

Oncolog, Volume 58, Number 07, July 2013, Zach Bohannan, Sunni Hosemann

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

• Treating Diabetes in Cancer Patients: Type 2 diabetes is a serious health concern for any patient-but when the patient also has cancer, diabetes may interfere with potentially life-saving cancer treatment
• INBRIEF: MET Protein May Serve as a Biomaker for a Treatment-Resistant Colorectal Cancer Subtype
• Compass: Penile Cancer- Although curable, localized or regional squamous cell carcinoma of the penis present treatment dilemmas
• HOUSE CALL: Stand Up for Your Health- Prolonged sitting may increase your risk for cancer and other disease

Altered Drainage Patterns In Patients With Melanoma And Previous Axillary Dissection., Caitlyn M. Johnson, Charles Intenzo, Michael Mastrangelo, Kendra Feeney, Adam C. Berger

Department of Surgery Faculty Papers

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously …

Caloric Restriction Augments Radiation Efficacy In Breast Cancer., Anthony D Saleh, Brittany A Simone, Juan Palazzo, Jason E Savage, Yuri Sano, Tu Dan, Lianjin Jin, Colin E Champ, Shuping Zhao, Meng Lim, Frederica Sotgia, Kevin Camphausen, Richard G Pestell, James B Mitchell, Michael P Lisanti, Nicole L Simone

Kimmel Cancer Center Faculty Papers

Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories …

Dynamic Functions Of Rhoa In Tumor Cell Migration And Invasion, Kathleen L. O'Connor, Min Chen

Markey Cancer Center Faculty Publications

RhoA is one of the more extensively studied members of the Rho family of small GTPase where it is most readily recognized for its contributions to actin-myosin contractility and stress fiber formation. Accordingly, RhoA function during cell migration has been relegated to the rear of the cell where it mediates retraction of the trailing edge. However, RhoA can also mediate membrane ruffling, lamellae formation and membrane blebbing, thus suggesting an active role in membrane protrusions at the leading edge. With the advent of fluorescence resonance energy transfer (FRET)-based Rho activity reporters, RhoA has been shown to be active at the …

Breast Cancer Antiestrogen Resistance 3 (Bcar3) Promotes Cell Motility By Regulating Actin Cytoskeletal And Adhesion Remodeling In Invasive Breast Cancer Cells., Ashley L Wilson, Randy S Schrecengost, Michael S Guerrero, Keena S Thomas, Amy H Bouton

Department of Cancer Biology Faculty Papers

Metastatic breast cancer is incurable. In order to improve patient survival, it is critical to develop a better understanding of the molecular mechanisms that regulate metastasis and the underlying process of cell motility. Here, we focus on the role of the adaptor molecule Breast Cancer Antiestrogen Resistance 3 (BCAR3) in cellular processes that contribute to cell motility, including protrusion, adhesion remodeling, and contractility. Previous work from our group showed that elevated BCAR3 protein levels enhance cell migration, while depletion of BCAR3 reduces the migratory and invasive capacities of breast cancer cells. In the current study, we show that BCAR3 is …

Acetylation Of The Cell-Fate Factor Dachshund Determines P53 Binding And Signaling Modules In Breast Cancer., Ke Chen, Kongming Wu, Michael Gormley, Adam Ertel, Jing Wang, Wei Zhang, Jie Zhou, Gabriele Disante, Zhiping Li, Hallgeir Rui, Andrew A Quong, Steven B Mcmahon, Haiteng Deng, Michael P Lisanti, Chenguang Wang, Richard G Pestell

Department of Cancer Biology Faculty Papers

Breast cancer is a leading form of cancer in the world. The Drosophila Dac gene was cloned as an inhibitor of the hyperactive epidermal growth factor (EGFR), ellipse. Herein, endogenous DACH1 co-localized with p53 in a nuclear, extranucleolar compartment and bound to p53 in human breast cancer cell lines, p53 and DACH1 bound common genes in Chip-Seq. Full inhibition of breast cancer contact-independent growth by DACH1 required p53. The p53 breast cancer mutants R248Q and R273H, evaded DACH1 binding. DACH1 phosphorylation at serine residue (S439) inhibited p53 binding and phosphorylation at p53 amino-terminal sites (S15, S20) enhanced DACH1 binding. DACH1 …

Oncolog, Volume 58, Number 06, June 2013, Joe Munch, Amelia Scholtz, Luanne Jorewicz

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

• Addressing Emerging Survivorship Issues in Glioblastoma Patients: An increasing number of glioblastoma patients are becoming '' long-term'' survivors-living 3 or more years after diagnosis
• Prediction Tool Helps Determine Whether Older Breast Cancer Patients will benefit from Radiation: A statistical tool is now available to predict the likely individual benefit of radiation therapy for older women who have undergone breast-conserving surgery for breast cancer
• Sequential Multidrug Regiman May Offer an Alternative to Standard Cisplatin-Based Therapy for Urothelial Cancer: Cisplatin-based chemotherapy is the standard neoadjuvant treatment for high-risk, surgically resectable, invasive urothelial cancer. But some patients are not good candidates for this …

Establishment And Validation Of A Novel Fucci (Fluorescent Ubiquitination-Based Cell Cycle Indicator) In An In Vitro Chronic Myeloid Leukemia Model, Jane Marie Isquith

Master's Theses

The deregulation of the cell cycle is important in the leukemic transformation and in the continued discovery of more efficient targeted therapies. After elucidation of the role of the RNA editor ADAR1 in the malignant reprogramming of Chronic Myeloid Leukemia (CML) progenitors to leukemia stem cells (LSCs) during the chronic phase to blast crisis stages of the disease, current research seeks to uncover the mechanism of action of ADAR1 in this process. To study the potential role ADAR1 plays in the changes to cell cycle during this disease progression, a novel Fucci (fluorescent ubiquitination-based cell cycle indicator) system was introduced …

Uv Radiation And The Skin, John A. D'Orazio, Stuart G. Jarrett, Alexandra Amaro-Ortiz, Timothy Scott

Toxicology and Cancer Biology Faculty Publications

UV radiation (UV) is classified as a "complete carcinogen" because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and …

Single Centre Study Of Using Bendamustine In The Treatment Of B-Cell Malignancies, Asif Husain Osmani, Nehal Masood

Department of Radiation Oncology

Objective: To evaluate the experience of bendamustine in the treatment of B-cell malignancies at a tertiary care centre.Methods: The retrospective descriptive analysis included data of all adult patients with B-cell malignancies treated with bendamustine from 2009 to 2011 at the Aga Khan University Hospital, Karachi. Data was analysed using SPSS 17.0. Frequencies and percentages were computed for baseline characteristics, responses and toxicities.Results: Of the 19 patients 15 (79%) were males and 4 (21%) were females.The mean age was 59.53+/-12.14 (with a range of 46-86). Eight (42%) had follicular lymphoma, 6 (32%) had mantle cell lymphoma, 2 (11%) had diffuse large …

Peripheral T-Cell Lymphomas: A Review Of Current Approaches And Hopes For The Future., Alan P Skarbnik, Meher Burki, Barbara Pro

Kimmel Cancer Center Faculty Papers

Peripheral T-cell lymphomas (PTCL) are a diverse group of lymphoproliferative disorders, which share a common denominator of overall poor prognosis, with few exceptions. In this article, the authors review current standard of care approaches for the treatment of PTCLs, the role of stem-cell/bone marrow transplantation, and current developments in novel targeted therapies.

Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …

Body Talk I: Habituation To Bodily Changes After Breast Surgery In Women, Jenny Slatman

Future Directions in Feminist Phenomenology

No abstract provided.

Fearless: Kevin Lugo, Kevin B. Lugo

SURGE

This summer, recent graduate Kevin Lugo will bike over 4,000 miles across the country to benefit the Ulman Cancer Fund for Young Adults. His choice to bike for seventy days from Baltimore to Seattle makes him fearless! His goal is to raise $7,476 for the organization, and he reached that goal last night (although more donations are always welcome in support of fighting cancer)! Kevin explains that when he studied abroad in Denmark in the fall of 2011, he “fell in love with sustainable transportation, especially cycling.” Not only does his fearless endeavor raise money to fight cancer, but he …

Late Effects Of Childhood Cancer : Implications For Child Life Specialists, Meghan Brewer

Graduate Student Independent Studies

No abstract provided.

Flurbiprofen Benzyl Nitrate (Nbs-242) Inhibits The Growth Of A-431 Human Epidermoid Carcinoma Cells And Targets Β-Catenin, Niharika Nath, Xiaoping Liu, Lloydine Jacobs, Khosrow Kashfi

Publications and Research

Background: The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer.

Methods: We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3.

Results: NBS-242 inhibited the growth of …

Oncolog, Volume 58, Number 05, May 2013, Jill Delsigne, Bryan Tutt

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

• Robotic Surgery Makes Tissue Harvest for Breast Reconstruction Less Invasive: A new minimally invasive robotic procedure enables surgeons to harvest latissimus dorsi muscle flaps for breast reconstruction with less scarring and discomfort than traditional techniques
• Diagnosis and Treatment of Invasive Fungal Infections in patients with Hematological Malingnancies: Invasive fungal infections are important causes of morbidity and death for patients with hematological malignancies. Although much progress has been made in the management of opportunistic fungal infections, their diagnosis and treatment remain a challenge
• INBRIEF: Beta-Blocker Use Associated With Higher Survival Rates in Lung Cancer Patients Receiving Radiation Therapy/ Selumetinib Shows Promise …

The Impact Of Family History On Medullary Thyroid Cancer In Men2a Patients, Nicole D. Mohrbacher

Dissertations and Theses (Open Access)

The American Thyroid Association recently classified all MEN2A-associated codons into increasing risk levels A-C and stated that some patients may delay prophylactic thyroidectomy if certain criteria are met. One criterion is a less aggressive family history of MTC but whether families with the same mutated codon have variable MTC aggressiveness is not well described. We developed several novel measures of MTC aggressiveness and compared families with the same mutated codon to determine if there is significant inter-familial variability. Pedigrees of families with MEN2A were reviewed for codon mutated and proportion of RET mutation carriers with MTC. Individuals with MTC were …

Novel Therapeutic Targets Identified By High-Throughput Technologies For Triple-Negative Breast Cancer, Christine Shiang

Dissertations and Theses (Open Access)

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to …

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey

Dissertations and Theses (Open Access)

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.

HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.

METHODS: 253 individuals with an …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Alpcs(2a)-Mediated Photochemical Internalization Of Bleomycin And Concurrent Hyperthermia Of Multicellular Tumor Spheroids, Aaron Andersen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Treatments for glioblastoma multiforme and invasive ductal carcinoma involve surgical resection and adjuvant or concurrent targeted therapies. The goal of the secondary treatment is to reduce the cancer cells in the resection margin and other areas of suspected involvement. Photochemical internalization is a targeted therapy using light to activate photosensitizers embedded in cellular structures to improve the delivery of macromolecules within the cell.

In a previous study, optimized treatment parameters including radiant exposure, and irradiance, concentration of AlPcS(2a), temperature, and the concentration of bleomycin were determined for human ACBT glioma multicell spheroids. The current study investigates the effectiveness of the …

Coping With Pediatric Cancer: Conversational Methods Utilized By Parents And Children When Dealing With Pediatric Cancer, Chelsi Morgan Walls

Graduate Research Symposium (2010 - 2017)

This thesis sought to analyze how parents communicate with their child regarding pediatric cancer treatments. When dealing with pediatric cancer, it is vital that parents and their child communicate about the illness in order to effectively cope with the cancer. Using Uncertainty Management Theory, along with sub-concepts of the theory (i.e., appraisals, inferences, and illusions), this thesis sought to discover which coping mechanism (i.e., affect-management or buffering) would be chosen to manage the illness. Under UMT, appraisals were assessed, resulting in positive and negative appraisal, which indicated whether the individual handled the issue with either an inference based on general …