Medical Specialties Commons^™

Nuclear Factor Of Activated T-Cells 5 Increases Intestinal Goblet Cell Differentiation Through An Mtor/Notch Signaling Pathway, Yuning Zhou, Qingding Wang, Heidi L. Weiss, B. Mark Evers

Markey Cancer Center Faculty Publications

The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis that is regulated by multiple signaling pathways. Previously, we have shown that the nuclear factor of activated T-cells 5 (NFAT5) is involved in the regulation of intestinal enterocyte differentiation. Here we show that treatment with sodium chloride (NaCl), which activates NFAT5 signaling, increased mTORC1 repressor regulated in development and DNA damage response 1 (REDD1) protein expression and inhibited mTOR signaling; these alterations were attenuated by knockdown of NFAT5. Knockdown of NFAT5 activated mammalian target of rapamycin (mTOR) signaling and significantly inhibited REDD1 mRNA expression and protein expression. Consistently, …

Physicians' Attitudes About Recommending Surgery For Early Stage Lung Cancer And Possible Reasons For Racial Disparities, Franklin R. Mcguire

Journal of Health Disparities Research and Practice

PHYSICIANS’ ATTITUDES ABOUT RECOMMENDING SURGERY FOR EARLY STAGE LUNG CANCER AND POSSIBLE REASONS FOR RACIAL DISPARITIES

ABSTRACT

Purpose: Patient refusal for lung cancer surgery is significant, but other factors, such as negative framing of the treatment discussion, may be involved. Physician attitudes could influence the nuances of and therefore the conclusions of these discussions. We determined physicians’ attitudes and the influence it has on possible decisions against lung cancer surgery, particularly surgical rates for blacks, using a companion survey.

Methods: The study is a prospective, multicenter observational trial conducted at five sites in North and South Carolina from December …

Oncolog, Volume 59, Number 09, September 2014, Stephanie Deming, Bryan Tutt, Joe Munch, Jill Delsigne

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

• Biomarker-Driven Clinical Trials may Improve Personalized Treatment for Patients With Lung Cancer: Innovative clinical trials that assign patients to treatment arms based on tumor biomarkers could lead to increase treatment options for patients with lung cancer
• New Antibody-Chemotherapy Combinations Show Promise Against Acute Lymphoblastic Leukemia: Two investigational agents-inotuzumab and ofatumumab-shows promise when combined with cytotoxic chemotherapy drugs for the treatment of acute lymphoblastic leukemia (ALL) in adults
• Deep Inspiration Breath Hold Protects Against Radiation-Induced Cardiotoxicity in Patients With Left-Sided Breast cancers: Patients with lest-sided breast cancers have an increased risk of heart damage from adjuvant radiation therapy given after lumpectomy …

Survival Advantage Associated With Decrease In Stage At Detection From Stage Iiic To Stage Iiia Epithelial Ovarian Cancer, John Hoff, Lauren Baldwin, Jason Lefringhouse, Edward J. Pavlik, Rachel Miller, Christopher Desimone, Frederick Ueland, Thomas Tucker, Richard Kryscio, John R. Van Nagell Jr.

Markey Cancer Center Faculty Publications

Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor …

Fructose-2,6-Bisphosphate Synthesis By 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (Pfkfb4) Is Required For The Glycolytic Response To Hypoxia And Tumor Growth, Jason Chesney, Jennifer Clark, Alden C. Klarer, Yoannis Imbert-Fernandez, Andrew N. Lane, Sucheta Telang

Markey Cancer Center Faculty Publications

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than …

Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She

Markey Cancer Center Faculty Publications

The cap-dependent translation is frequently deregulated in a variety of cancers associated with tumor progression. However, the molecular basis of the translation activation for metastatic progression of cancer remains largely elusive. Here, we demonstrate that activation of cap-dependent translation by silencing the translational repressor 4E-BP1 causes cancer epithelial cells to undergo epithelial-mesenchymal transition (EMT), which is associated with selective upregulation of the EMT inducer Snail followed by repression of E-cadherin expression and promotion of cell migratory and invasive capabilities as well as metastasis. Conversely, inhibition of cap-dependent translation by a dominant active mutant 4E-BP1 effectively downregulates Snail expression and suppresses …

Cardio-Oncology: Success Breeds New Challenges, Opportunities, Charles A. Bomzer, Bijoy K. Khandheria

Journal of Patient-Centered Research and Reviews

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Diagnosis Of Chemotherapy-Induced Cardiotoxicity, Fausto Pizzino, Giampiero Vizzari, Charles A. Bomzer, Rubina Qamar, Scipione Carerj, Concetta Zito, Bijoy K. Khandheria

Journal of Patient-Centered Research and Reviews

Cardiotoxicity is a rising issue connected to use of chemotherapy and radiotherapy in the treatment of neoplastic diseases. Early diagnosis during follow-up is of paramount importance, and careful surveillance is recommended. Evaluation of left ventricular ejection fraction by echocardiography and nuclear medicine techniques is widely used in clinical practice; however, their sensitivity in detecting early cardiac damage is low. New instruments like speckle-tracking imaging, cardiac magnetic resonance and cardiac circulating biomarkers are available to clinicians to best evaluate the onset and progression of cardiotoxic effects, improving the therapeutic management and final outcome for the patient.

Cardiovascular Toxicity Of Common Chemotherapy Drugs Used To Treat Breast Cancer: An Overview, Charles A. Bomzer

Journal of Patient-Centered Research and Reviews

Treatment of breast cancer often exposes patients to many different drugs. Some of these drugs have toxic effects involving the cardiovascular system. This review provides an overview of the drugs most commonly used to treat breast cancer and their potential adverse impact on the cardiovascular system.

An Overview Of Cancer Rehabilitation And Exercise In The Literature: Promoting Increased Referrals To Improve Oncology Outcomes, Leslie J. Waltke

Journal of Patient-Centered Research and Reviews

Medical management for malignant neoplastic diseases includes surgery, chemotherapy, radiation, and hormonal and biological therapies. Each of these antineoplastic interventions has unique impacts on physiological, musculoskeletal and functional performance. Cancer rehabilitation is the area of physical medicine responsible for addressing impairments associated with cancer treatment and survivorship, advanced disease and end of life. Although it is expected that more than one-half of persons being treated for cancer will suffer moderate pain and physical and functional decline, and that most will describe fatigue, referrals to rehabilitation are traditionally low. Evidence suggests that referrals to rehabilitation before, during and after treatment for …

The Role Of Ape/Ref-1 In Hepatocellular Carcinoma Progression, Zhen Yang, Sun Yang, Bobbye J. Misner, Feng Liu-Smith, Frank L. Meyskens

Pharmacy Faculty Articles and Research

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell …

The Influence Of Race/Ethnicity And Place Of Service On Breast Reconstruction For Medicare Beneficiaries With Mastectomy, Tracy Onega, Julie Weiss, Karla Kerlikowske, Karen Wernli

Dartmouth Scholarship

Racial disparities in breast reconstruction for breast cancer are documented. Place of service has contributed to disparities in cancer care; but the interaction of race/ethnicity and place of service has not been explicitly examined. We examined whether place of service modified the effect of race/ethnicity on receipt of reconstruction. We included women with a mastectomy for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare claims, we determined breast reconstruction within 6 months. Facility characteristics included: rural/urban location, teaching status, NCI Cancer Center designation, cooperative oncology group membership, Disproportionate Share Hospital (DSH) status, and breast surgery volume. Using multivariable logistic …

Oncolog, Volume 59, Number 08, August 2014, Kathryn L. Hale, Bryan Tutt, Sunita Patterson, R. Molar-Candanosa

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

• Immune Checkpoint Inhibitors Show Promise Against Metastatic Renal Cell Carcinoma, Other Difficult-to-Treat Cancers: A decade ago, oncologists had little to offer most patients with metastatic renal cell carcinoma (RCC). However, a breakthrough discovery that has already changed the treatment of metastatic melanoma is showing promise against other metastatic cancers-including metastatic RCC-and giving patients new hope for long-term survival
• Clinical Study Offers Definitive Local Treatment of Bone Metastases from Breast Cancer: Metastatic breast cancer carries a poor prognosis, and most systemic treatments for metastatic disease aim to slow its progression rather than to cure it. In a select group of patients, …

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Rorα Binds To E2f1 To Inhibit Cell Proliferation And Regulate Mammary Gland Branching Morphogenesis, Gaofeng Xiong, Ren Xu

Markey Cancer Center Faculty Publications

Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC …

Novel Serum Biomarkers For Lung Cancer Early Diagnosis And Clinical Outcome, Fanmao Zhang

Dissertations and Theses (Open Access)

The five-year survival rate for all stages of lung cancer combined is only 17%, which has changed little over the past 40 years. Despite the tremendous efforts made, serum biomarkers with clinical utility for lung cancer early detection and clinical outcome prediction are still lacking. Metabolic alterations have been recognized as an emerging hallmark of cancer. We aimed to investigate the metabolic changes associated with lung cancer and to identify novel clinically applicable serum biomarkers for lung cancer early diagnosis and clinical outcome.

Serum metabolites are potential biomarkers for lung cancer early detection. We first performed global metabolomic profiling followed …

Parp-2 And Parp-3 Are Selectively Activated By 5' Phosphorylated Dna Breaks Through An Allosteric Regulatory Mechanism Shared With Parp-1., Marie-France Langelier, Amanda A Riccio, John M Pascal

Department of Biochemistry and Molecular Biology Faculty Papers

PARP-1, PARP-2 and PARP-3 are DNA-dependent PARPs that localize to DNA damage, synthesize poly(ADP-ribose) (PAR) covalently attached to target proteins including themselves, and thereby recruit repair factors to DNA breaks to increase repair efficiency. PARP-1, PARP-2 and PARP-3 have in common two C-terminal domains-Trp-Gly-Arg (WGR) and catalytic (CAT). In contrast, the N-terminal region (NTR) of PARP-1 is over 500 residues and includes four regulatory domains, whereas PARP-2 and PARP-3 have smaller NTRs (70 and 40 residues, respectively) of unknown structural composition and function. Here, we show that PARP-2 and PARP-3 are preferentially activated by DNA breaks harboring a 5' phosphate …

Gate Monte Carlo Simulations In A Cloud Computing Environment, Blake Austin Rowedder

UNLV Theses, Dissertations, Professional Papers, and Capstones

The GEANT4-based GATE is a unique and powerful Monte Carlo (MC) platform, which provides a single code library allowing the simulation of specific medical physics applications, e.g. PET, SPECT, CT, radiotherapy, and hadron therapy. However, this rigorous yet flexible platform is used only sparingly in the clinic due to its lengthy calculation time. By accessing the powerful computational resources of a cloud computing environment, GATE's runtime can be significantly reduced to clinically feasible levels without the sizable investment of a local high performance cluster. This study investigated a reliable and efficient execution of GATE MC simulations using a commercial cloud …

Synthesis And Characterization Of Novel Platinum(Ii) And Platinum(Iv) Complexes Containing 4,4′--Disubstituted--2,2′--Bipyridine Ligands For The Treatment Of Cancer, Van Vo

UNLV Theses, Dissertations, Professional Papers, and Capstones

Three series of platinum(II) and platinum(IV) complexes containing 4,4′-disubstituted-2,2′-bipyridine ligands have been synthesized and characterized by 1H NMR, 13C NMR spectroscopy, elemental analysis, mass spectroscopy, and differential scanning calorimetry measurements. The MTS cell proliferation assay was used to examine the in vitro anti-proliferative activities of these complexes in various human breast, lung, and prostate cancer cells. The cell's response to the complexes varies between different cell lines; however, the low EC₅₀ values determined from the MTS data indicate that several of the complexes are much more potent than cisplatin.

Flow cytometric analysis of selected compounds revealed induction of apoptosis …

Methylseleninic Acid Sensitizes Notch3-Activated Ovca429 Ovarian Cancer Cells To Carboplatin., Tiffany J. Tzeng, Lei Cao, Yangxin Fu, Huawei Zeng, Wen-Hsing Cheng

CALS Publications

Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein …

Gene Sleuth, Kevin Cool

Colby Magazine

Patricia Davis Murphy '68 tracks down a cancer-causing genetic mutation.

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …

Pharmacokinetics And Toxicity Of The Novel Oral Demethylating Agent Zebularine In Laboratory And Tumor Bearing Dogs, Christopher Michael Fulkerson

Open Access Theses

The aim of this thesis is to investigate the pharmacokinetics and toxicity of the novel oral demethylating agent zebularine (zeb) in laboratory dogs and tumor bearing dogs. This thesis focuses on the application of this therapeutic strategy in dogs with naturally occurring invasive transitional cell carcinoma (InvTCC), which serve as a relevant model of the human disease.

DNA hypermethylation in the promoter region is a common epigenetic change in cancer that silences tumor suppressor genes. Zeb is an oral cytidine analog that acts as a demethylating agent. Zeb has been investigated extensively in vitro as well as in mice, rodents …

Oncolog, Volume 59, Number 07, July 2014, Sarah Bronson, Joe Munch, Bryan Tutt, K. Stuyck

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

• Side Effects of Targeted Molecular Agents Vary According to Mechanism of Action: The main side effects of cytotoxic chemotherapy are notorious. But the side effects of newer, targeted molecular agents are less well known, so patients receiving such drugs may not know what to expect and may require additional guidance from physicians
• INBRIEF: Study Finds Less Frequent Bisphosphonate Treatment Equivalent to Standard Regimen
• RAS Mutation Status May predict Outcomes After Surgery for Colorectal Cancer Liver Metastases
• HPV Test Does Not Replace Pap Test for Cervical cancer Screening: The recent approval of a human papillomavirus (HPV) test for cervical cancer screening …

Evaluation Of Ct Images Created Using A New Metal Artifact Reduction Reconstruction Algorithm For Radiation Therapy Treatment Planning, John Niemkiewicz, Andrew G. Palmiotti, Marc S. Miner, Lee E. Stunja, Jenelle Bergene

Department of Radiation Oncology

No abstract provided.

Family-Specific, Novel, Deleterious Germline Variants Provide A Rich Resource To Identify Genetic Predispositions For Brcax Familial Breast Cancer., Hongxiu Wen, Yeong C. Kim, Carrie Snyder, Fengxia Xiao, Elizabeth A. Fleissner, Dina Becirovic, Jiangtao Luo, Bradley Downs, Simon Sherman, Kenneth Cowan, Henry T. Lynch, San Ming Wang

Journal Articles: Eppley Institute

BACKGROUND: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide …

Metastatic Angiosarcoma And Kasabach-Merritt Syndrome, Suleiman Massarweh, Aun Munis, Rouzan Karabakhtsian, Edward Romond, Jessica Moss

Internal Medicine Faculty Publications

Angiosarcomas are exceedingly rare tumors that are often difficult to diagnose. Exceptionally unusual is the presentation of these tumors with Kasabach-Merritt Syndrome, a curious form of intratumoral coagulation that can be impossible to distinguish from intravascular coagulation, which is more common. Instant recognition of this clinical association can help making a prompt diagnosis and timely initiation of therapy.

Heuristic Modeling Of Carcinogenesis For The Population With Dichotomous Susceptibility To Cancer: A Pancreatic Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool) of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i) determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate) from the observed hazard rate in the …

The Tumor Suppressive Role Of Camk2n1 In Castration-Resistant Prostate Cancer., Tao Wang, Zhuo Liu, Shuiming Guo, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Shaohua Xu, Liping Wang, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen

Department of Cancer Biology Faculty Papers

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell …

Kids Alive! Support For Children Of Parents With Cancer: An Exemplar Program For Children Of Parents With Cancer, Shane Spears

Graduate School of Professional Psychology: Doctoral Papers and Masters Projects

Cancer in a parent or caregiver is an event that affects the whole family. The roles and responsibilities of the diagnosed parent, as well as those of each family member, are affected at the time of diagnosis and throughout the progression of the illness. According to the American Cancer Society, there will be an estimated 1,665,540 new cancer cases diagnosed and 585,720 cancer deaths in 2014. This staggering statistic means there are a number of cancer diagnoses that will directly affect thousands of parents and their children. Past research suggests this upheaval in the system is particularly stressful on children …