Medical Specialties Commons^™

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

Dicer1 Regulated Let-7 Expression Levels In P53-Induced Cancer Repression Requires Cyclin D1., Xin Sun, Shou-Ching Tang, Chongwen Xu, Chenguang Wang, Sida Qin, Ning Du, Jian Liu, Yiwen Zhang, Xiang Li, Gang Luo, Jie Zhou, Fei Xu, Hong Ren

Department of Cancer Biology Faculty Papers

Let-7 miRNAs act as tumour suppressors by directly binding to the 3'UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback …

Quantifying Unnecessary Normal Tissue Complication Risks Due To Suboptimal Planning: A Secondary Study Of Rtog 0126., Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.

METHODS AND MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative …

Oncolog, Volume 60, Number 06, June 2015, Bryan Tutt, Joe Munch, U. Arizor

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

• New Breast Imaging Modalities Show promise for Cancer Screening and Staging: New technology to supplement digital mammography may improve breast cancer screening and diagnosis. Although some of these new imaging modalities are still under development, others are already in clinical use as adjuncts to mammography for breast cancer screening and staging.
• Addressing Sexual Dysfunction in Cancer Survivors: Cancer treatments carry a host of side effects that can affect patients' ability to have and enjoy sex. The sexual dysfunction arising from these side effects, which include functional changes, can often be addressed, but uncovering sexual dysfunction can prove challenging.
• HOUSE CALL: …

Salvage Brachytherapy In Combination With Interstitial Hyperthermia For Locally Recurrent Prostate Carcinoma Following External Beam Radiation Therapy: A Prospective Phase Ii Study., Andrzej M Kukiełka, Vratislav Strnad, Paul R. Stauffer, Tomasz Dąbrowski, Marcin Hetnał, Damian Nahajowski, Tomasz Walasek, Piotr Brandys, Robert Matys

Department of Radiation Oncology Faculty Papers

Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear …

Depression Among Asian-American Adults In The Community: Systematic Review And Meta-Analysis., Hee Jun Kim, Eunmi Park, Carla L Storr, Katherine Tran, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

OBJECTIVES: In this systematic review, we provide an overview of the literature on depression among Asian-Americans and explore the possible variations in depression prevalence estimates by methodological and demographic factors.

METHODS: Six databases were used to identify studies reporting a prevalence estimate for depression in Asian-American adults in non-clinical settings. Meta-analysis was used to calculate pooled estimates of rates of depression by assessment type. Statistical heterogeneity was assessed for subgroup analyses by gender, age, ethnicity, and other participant characteristics.

RESULTS: A total of 58 studies met the review criteria (n = 21.731 Asian-American adults). Heterogeneity across the studies was considerably …

Improving Hand Hygiene Compliance To Reduce Clabsi Rate In Oncology Icu, Lorenzo D. San Pedro

Master's Projects and Capstones

The aim of this project is to reduce the rate of central line associated blood stream infection (CLABSI) occurrence in oncology ICU by 50% by the last quarter of 2015. This study was conducted in ICU to assess adherence to the facility’s hand hygiene (HH) protocol among the staff nurses and allied healthcare workers. The facility is best known as a non-profit cancer treatment center and designated as a Comprehensive Cancer Center. Evidence showed that hand hygiene is the most effective way of preventing CLABSI, one of the most common types of infection in ICU microsystem. The project utilized The …

Undifferentiated Carcinoma With Osteoclast-Like Giant Cells Of The Pancreatic Tail, Patrick Hickey Do, Ranjit R. Nair Md, Victoria A. Loven Md, Jeffrey Brodsky Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

End-Of-Life Care: Crossing The Bridge From Treatment To Support, Martha C. Romney Bsn, Ms, Jd, Mph

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

The Endogenous Cell-Fate Factor Dachshund Restrains Prostate Epithelial Cell Migration Via Repression Of Cytokine Secretion Via A Cxcl Signaling Module., Ke Chen, Kongming Wu, Xuanmao Jiao, Liping Wang, Xiaoming Ju, Min Wang, Gabriele Disante, Shaohua Xu, Qiong Wang, Kevin Li, Xin Sun, Chongwen Xu, Zhiping Li, Mathew C. Casimiro, Adam Ertel, Sankar Addya, Peter Mccue, Michael P. Lisanti, Chenguang Wang, Richard J. Davis, Graeme Mardon, Richard Pestell

Department of Cancer Biology Faculty Papers

Prostate cancer is the second leading form of cancer-related death in men. In a subset of prostate cancer patients, increased chemokine signaling IL8 and IL6 correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are produced by prostate epithelial cells and promote prostate cancer cell invasion; however, the mechanisms restraining prostate epithelial cell cytokine secretion are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited CRPC tumor growth in mice. Using Dach1(fl/fl)/Probasin-Cre bitransgenic mice, we show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to …

Treatment Plan Adherence To Guidelines In Senior Adult Oncology Patients, Amy R. Mackenzie, Md, Andrea M. Barsevick, Phd, Ronald Myers, Phd, Ludmila De Oliveira Koch, Md, Scott W. Keith, Phd, Thomas Wolf, Ma, James Cocroft, Ma, Joshua Schoppe, Mph, Ulysses Williams Iii, Andrew Chapman, Do

Department of Medical Oncology Faculty Papers

Materials & Methods:

• Review of 287 records
• Patients ≥ 65 years old with new diagnosis of cancer
• Seen by 6, dual-boarded hematologists/ oncologists practicing in an urban academic cancer center
• Treatment plans compared to national guidelines to determine plan adherence status
• Patients were recommended:

Adherent plan (AP) or Non-adherent plan (N-AP)

Clinical Applications Of A Combination Chemotherapy Using 8-Chloro Camp And 8-Chloro Adenosine, Erik Munoz, Andrea Saich, Andrew Cox, Yu-An Peter Chang

Student Scholar Symposium Abstracts and Posters

Dr. Cho-Chung from the NIH first thought to use halogenated cAMP derivatives as competitive inhibitors of cAMP to slow down cancer cell mitosis. While the iodine and bromine substituted versions showed very little therapeutic actions, 8-Chloro cAMP has been shown to have strong anti-cancer effects. This has been shown in the phase II clinical trials this drug has undergone. However, these trials have had issues with solubility and toxicity. The drug is similar to vitamin C and is excreted quickly. Scientists tried to overcome this by using a peristaltic pump to give patients a continuous dosage, but this proved too …

A Comparison Of The Scapular Flip Test Between Women With Breast Cancer And Healthy Controls, Mary Insana Fisher, Lucinda Pfalzer, Ellen W. Levy, Shana Harrington, Lynn H. Gerber, Nicole L. Stout

Physical Therapy Faculty Publications

Presentation at the World Confederation for Physical Therapy Congress, held May 1-4, 2015, in Singapore.

Background: The Scapular Flip test was designed to screen for spinal accessory nerve palsy. The spinal accessory nerve can be damaged in breast cancer surgery and treatment, resulting in scapular dyskinesis and upper limb (UL) impairment in women with breast cancer (BC). This test could be useful to screen for UL impairment in BC.

Purpose: The purpose of this study was to describe shoulder impairments as defined by a positive Flip Test in a group of women with BC at baseline, 1-3 months, and 12+ …

Consequence Of The Tumor-Associated Conversion To Cyclin D1b., Michael A Augello, Lisa D Berman-Booty, Richard Carr, Akihiro Yoshida, Jeffry L Dean, M J Schiewer, Felix Y Feng, Scott A Tomlins, Erhe Gao, Walter J Koch, Jeffrey L Benovic, John Alan Diehl, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Clinical evidence suggests that cyclin D1b, a variant of cyclin D1, is associated with tumor progression and poor outcome. However, the underlying molecular basis was unknown. Here, novel models were created to generate a genetic switch from cyclin D1 to cyclin D1b. Extensive analyses uncovered overlapping but non-redundant functions of cyclin D1b compared to cyclin D1 on developmental phenotypes, and illustrated the importance of the transcriptional regulatory functions of cyclin D1b in vivo. Data obtained identify cyclin D1b as an oncogene, wherein cyclin D1b expression under the endogenous promoter induced cellular transformation and further cooperated with known oncogenes to promote …

Oncolog, Volume 60, Number 05, May 2015, Sarah Bronson, Bryan Tutt, U. Arizor

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

• Algorithm for Treating Advanced Ovarian Cancer Increases Complete Resection Rate: Most ovarian cancers have spread beyond the ovary by the time they are diagnosed, and they often recur even after responding to primary treatment. Researchers at The University of Texas MD Anderson Cancer Center aim to improve patient outcomes by changing the standard approach to newly diagnosed advanced ovarian cancer.
• Clinical Trials Explore Systemic Treatments for Brain Metastases from Breast Cancer: Brain metastases from breast cancer are difficult to treat because many of the systemic drugs that are effective against breast cancer cannot cross the blood-brain barrier. But researchers at …

Comparison Of Survival In Patients With T Cell Lymphoma After Autologous And Allogeneic Stem Cell Transplantation As A Frontline Strategy Or In Relapsed Disease., Amer Beitinjaneh, Rima M. Saliba, L. Jeffrey Medeiros, Francesco Turturro, Gabriela Rondon, Martin Korbling, Luis Fayad, Michelle A. Fanale, Amin M. Alousi, Paolo Anderlini, Oran Betul, Uday R. Popat, Barbara Pro, Issa F. Khouri

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

We studied the roles of autologous (A) and allogeneic (allo) stem cell transplantation (SCT) in the treatment of 134 patients with T cell lymphoma (TCL) at our center. For frontline SCT, 58 patients were studied. The 4-year overall survival (OS) rates for ASCT (n = 47; median age, 49 years) and alloSCT (n = 11; median age, 55 years) groups were 76% and 54%, respectively (P > .05). The 4-year OS rates for first complete remission (CR1) patients were 84% and 83%, respectively. For SCT for relapsed disease, 76 patients were studied (41 with ASCT and 35 with alloSCT). The 4-year …

Serum Omentin As A Potential Biomarker For Complex Atypical Hyperplasia And Endometrioid Endometrial Adenocarcinoma, Laura L. Holman Md

Dissertations and Theses (Open Access)

Obesity is a significant risk factor for endometrial cancer, the most common gynecologic malignancy in the United States, but much remains unclear about the relationship between obesity-related factors and the development of endometrial cancer. Omentin, a recently discovered adipokine, has been shown to be present in lower levels in patients who are obese and/or insulin resistant. A case-control study was conducted using the serum of 140 women with endometrial cancer and 75 women with endometrial hyperplasia who were matched 1:1 based on body mass index (BMI) and menopausal status to women with no history of endometrial cancer (controls). The concentration …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations and Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …

Transarterial Chemoembolization Is Ineffective For Neuroendocrine Tumors Metastatic To The Caudate Lobe: A Single Institution Review., Lawrence A Shirley, Megan Mcnally, Ravi Chokshi, Natalie Jones, Patrick Tassone, Gregory Guy, Hooman Khabiri, Carl Schmidt, Manisha Shah, Mark Bloomston

Oncology Articles

BACKGROUND: Caudate lobe liver metastases occur commonly in patients with neuroendocrine tumors. It is unknown, however, how these lesions respond to regional therapy and how their presence impacts outcomes. We reviewed our experience treating these lesions using transarterial chemoembolization (TACE).

METHODS: We reviewed radiographic response to TACE in 86 patients with metastatic neuroendocrine tumors to the liver. We determined the impact of caudate lesions on outcomes in comparison to the cohort of patients without caudate lesions, as well as response of caudate lesions to TACE versus lesions elsewhere in the liver.

RESULTS: Caudate lesions were identified in 45 (52%) patients. …

Cancer Associated Fibroblast Derived Angiogenic Factor Mfap5 In Ovarian Cancer Progression, Sze Lee Cecilia Leung

Dissertations and Theses (Open Access)

Advanced stage ovarian cancer is the most lethal gynecologic malignancy. No major improvement on patient survival has been achieved in the past decade. Therefore, identification of predictive or prognostic markers and further understanding of the molecular mechanisms in ovarian cancer progression are of paramount importance.

While cancer cells have always been the targets for the identification of prognostic and predictive markers, the potential for developing new diagnosis and treatments based on the tumor supporting stromal microenvironment is relatively unexplored. Using transcriptome profiling analysis on microdissected stromal and epithelial components of normal and malignant ovarian tissues, we identified a gene signature …

Evaluating The Nccn Clinical Criteria For Hereditary Breast And Ovarian Cancer Syndrome Genetic Testing, Caiqian Wu

Dissertations and Theses (Open Access)

Hereditary Breast and Ovarian Cancer (HBOC) syndrome predisposes females with a BRCA1 or BRCA2 mutation to an up to 85% lifetime risk for breast cancer and an up to 40% lifetime risk for ovarian cancer. It is crucial for individuals with HBOC to be identified to allow for proper screening, management, and identification of at-risk family members in order to reduce mortality. The National Comprehensive Cancer Network (NCCN) has established clinical guidelines for when to recommend BRCA1/2 testing. A retrospective chart review of 1123 M.D. Anderson Cancer Center breast cancer patients was performed in order to evaluate the positive predictive …

Gene Set Analysis Of Post-Lactational Mammary Gland Involution Gene Signatures In Inflammatory And Triple Negative Breast Cancer, Arvind Bambhroliya

Dissertations and Theses (Open Access)

With each cycle of pregnancy and lactation, the mammary gland undergoes dramatic changes. Clarkson et al. (2004) and Stein et al. (2004) conducted a detailed analysis of these changes in the mouse mammary gland. Their results showed that tissue remodeling during post-lactational involution period mimics wound healing and tumorigenesis like pathological conditions. This indicates that post-lactational involution may create the microenvironment that initiates the development of precancerous mammary cells and promotes the progression of precancerous cells into cancer cells. Moreover, epidemiological studies have found that triple-negative (TN) breast cancer (BC) is associated with lower frequency and duration of breastfeeding compared …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations and Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

Killer Cell Activation By A Novel Multifunctional Protein: An Immuno/Gene Therapy For Cancer, Ashlee Tietje

All Dissertations

One of the characteristics of advanced tumors is the evasion of the immune system. There are multiple methods that tumor cells employ to achieve this including reducing the expression of activating ligands on the cell surface and a shift in the tumor microenvironment toward pro-tumor cytokines. The purpose of this research is to develop a novel bifunctional fusion protein that will target these two deficiencies in the tumor microenvironment and activate killer cells that are already present. The proposed protein combines the extracellular domain of a ligand for the killer cell activating receptor NKG2D and Interleukin-12 (IL-12). It is hypothesized …

A Special Report Of Current State Of The Medical Physicist Workforce - Results Of The 2012 Astro Comprehensive Workforce Study, Erli Chen, Anna Arnone, Jussi K. Sillanpää, Yan Yu, Michael D. Mills

Department of Radiation Oncology Faculty Papers

No abstract provided.

Flattening Filter-Free Accelerators: A Report From The Aapm Therapy Emerging Technology Assessment Work Group, Ying Xiao, Stephen F. Kry, Richard A. Poppel, Ellen D. Yorke, Niko Papanikolaou, Sotirios Stathakis, Ping Xia, Saiful Huq, John E. Bayouth, James Galvin Phd, Fang-Fang Yin

Department of Radiation Oncology Faculty Papers

No abstract provided.

Local Modulation And Measurement Of Macrophage-Derived Bioactive Proteins From Implanted Biomaterials In Rat, Geetika Bajpai

Graduate Theses and Dissertations

Fibrosis around the implanted medical devices is a severe problem that can plague long-term device reliability. Activation of macrophage phenotype (macrophage polarization) has emerged as a new and possible means for reducing fibrosis in the fields of biomaterials and regenerative medicine. Macrophages are phagocytic cells that respond to microenvironmental cues that direct their phenotype. Macrophage activation has been widely studied in mouse and human in the context of tumor biology, yet little information is available regarding how macrophage activation could be used in a biomaterials context. Further, rats rather than mice are the common subjects in biomaterials experiments. A significant …

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

Kinase-Independent Role Of Cyclin D1 In Chromosomal Instability And Mammary Tumorigenesis., Mathew C Casimiro, Gabriele Disante, Marco Crosariol, Emanuele Loro, William Dampier, Adam Ertel, Zuoren Yu, Elizabeth A Saria, Alexandros Papanikolaou, Z Li, Chenguang Wang, Sankar Addya, Michael P. Lisanti, Paolo Fortina, Robert D Cardiff, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1-/- mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led …

Translation Initiation Complex Eif4f Is A Therapeutic Target For Dual Mtor Kinase Inhibitors In Non-Hodgkin Lymphoma., Christos Demosthenous, Jing Jing Han, Mary J Stenson, Matthew J Maurer, Linda E Wellik, Brian Link, Kristen Hege, Ahmet Dogan, Eduardo Sotomayor, Thomas Witzig, Mamta Gupta

Medicine Faculty Publications

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor …