Medicine and Health Sciences Commons^™

The Role Of Niacinamide In Skin Cancer Risk Reduction, Britny Ruilova Tellez

Doctor of Medical Science (DMSc)

The contents of this article are the author’s original unpublished findings.

Background: Each year, approximately 6 million Americans are treated for skin cancer, resulting in a total annual medical expense of $8.9 billion 1. The two most common types of skin cancer are basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC)2. The metastatic potential of these cancers is minimal; however, their treatment may involve severe scarring and disfigurement2. In contrast, melanoma is an aggressive skin malignancy that grows rapidly and can metastasize in a quick manner2. Risk factors of these skin cancers include UV exposure, fair skin complexions, …

Fargesin Inhibits Egf-Induced Cell Transformation And Colon Cancer Cell Growth By Suppression Of Cdk2/Cyclin E Signaling Pathway, Ga-Eun Lee, Cheol-Jung Lee, Hyun-Jung An, Han Chang Kang, Hye Suk Lee, Joo Young Lee, Sei-Ryang Oh, Sung-Jun Cho, Dae Joon Kim, Yong-Yeon Cho

School of Medicine Publications and Presentations

Although the lignan compound fargesin is a major ingredient in Shin-Yi, the roles of fargesin in carcinogenesis and cancer cell growth have not been elucidated. In this study, we observed that fargesin inhibited cell proliferation and transformation by suppression of epidermal growth factor (EGF)-stimulated G₁/S-phase cell cycle transition in premalignant JB6 Cl41 and HaCaT cells. Unexpectedly, we found that signaling pathway analyses showed different regulation patterns in which fargesin inhibited phosphatidylinositol 3-kinase/AKT signaling without an alteration of or increase in mitogen activated protein kinase (MAPK) in JB6 Cl41 and HaCaT cells, while both signaling pathways were abrogated by …

Apc-Β-Catenin-Tcf Signaling Silences The Intestinal Guanylin-Gucy2c Tumor Suppressor Axis., Erik S Blomain, Jeffrey A Rappaport, Amanda M Pattison, Babar Bashir, Ellen Caparosa, Jonathan Stem, Adam E Snook, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation …

Deployment And Travel Medicine Knowledge, Attitudes, Practices, And Outcomes Study (Kapos): Malaria Chemoprophylaxis Prescription Patterns In The Military Health System, Patrick W. Hickey, Indrani Mitra, Jamie Fraser, David Brett-Major, Mark S. Riddle, David R. Tribble

Journal Articles: Epidemiology

The Deployment and Travel Medicine Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS) examines the integrated relationship between provider and patient inputs and health outcomes associated with travel and deployments. This study describes malaria chemoprophylaxis prescribing patterns by medical providers within the U.S. Department of Defense's Military Health System and its network of civilian healthcare providers during a 5-year period. Chemoprophylaxis varied by practice setting, beneficiary status, and providers' travel medicine expertise. Whereas both civilian and military facilities prescribe an increasing proportion of atovaquone-proguanil, doxycycline remains the most prevalent antimalarial at military facility based practices. Civilian providers dispense higher rates of …

Risk Mitigation For Travelers: Managing Endemic And Emerging Threats, Shannon M. Wood, David Brett-Major

Journal Articles: Epidemiology

International travel continues to increase in numbers and complexity. Despite the availability of pretravel health advice, travelers remain at risk for exposure to common organisms as well as emerging pathogens. With low rates of travel clinic utilization, it is important for the general practitioner to remain aware of the importance of travel health, risk factors unique to individual patients, and evolving threats. This review highlights important considerations when evaluating ill travelers, incorporating emerging infectious threats.

Harnessing The Gatekeepers Of Glucocorticoids For Chemoprevention Of Non-Melanoma Skin Cancer, Anna M. Mancha-Ramirez, Xiaoyu Yang, Huiyun Liang, Jacob Junco, Kevin P. Lee, Sarah F. Bovio, Maricruz Espinoza, Julia Wool, Dae Joon Kim

School of Medicine Publications and Presentations

Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients suffer from tissue damage, scarring, or even disfigurement; thus, there is a need for chemopreventive approaches. Because of the complex interplay between glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role of 11β-hydroxysteroid dehydrogenase 1 and 2 (11βHSD1 and 2) in regulating GCs during skin cancer development and progression. 11βHSDs modulate the activation of GCs in a tissue-specific manner and have been reported to play a role in development and progression of other types of cancer, but their role has not yet been reported in NMSC. Here, we …

Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li

University of the Pacific Theses and Dissertations

Benzo[a]pyrene (BaP), is one of the most potent mutagens and carcinogens known. It requires metabolic activation through cytochrome P450 (CYP)1A1 to yield the ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to DNA and form predominantly covalent (+) trans adducts at the N2 position of guanine causing DNA damage. Rutaecarpine (RTC) is an herbal medicine that has been used to treat several diseases such as headache, hypertension, gastrointestinal disorders, amenorrhea, and anti-inflammation. It has also been reported as a potent inducer of CYP enzymes, including CYP1A1, and CYP1A2. The mechanisms underlying up-regulation of CYP1A1 by RTC is dependent on aryl …

P-21 Activated Kinase As A Molecular Target For Chemoprevention In Diabetes, Kyle Dammann, Vineeta Khare, Clyde Coleman, Henrik Berdel, Christoph Gasche

Surgery Faculty Publications

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling. Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here, we performed a mini-meta-analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways, to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using the online …

St-Producing E. Coli Oppose Carcinogen-Induced Colorectal Tumorigenesis In Mice., Peng Li, Jieru E. Lin, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may …

Myo-Inositol Reduces Β-Catenin Activation In Colitis, Emily M. Bradford, Corey A. Thompson, Tatiana Goretsky, Guang-Yu Yang, Luz M. Rodriguez, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

AIM

To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-catenin^S552 as a biomarker of recurrent dysplasia.

METHODS

We examined the effects of dietary myo-inositol treatment on inflammation, pβ-catenin^S552 and pAkt levels by histology and western blot in IL-10^-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-catenin^S552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia.

RESULTS

In mice, pβ-catenin^S552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a …

The Potential Role Of Nitric Oxide In Halting Cancer Progression Through Chemoprevention, Huzefa Vahora, Munawwar Ali Khan, Usama Alalami, Arif Hussain

All Works

Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment.

Novel Cellular Targets Of Aspirin In Chemoprevention Studies On P53, G6pd And C-Myc, Guoqiang Ai

Electronic Theses and Dissertations

Background

Aspirin has generated a significant interest in recent years as a potential chemopreventive agent supported by strong evidence from epidemiological data; however, the mechanisms are not well understood. The objective of this dissertation is to identify novel cyclooxygenase (COX)-independent pathways by which aspirin exerts its anticancer effects in epithelial cancer cell lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …

Induction Of Synthetic Lethality In Mutant Kras Cells For Non-Small Cell Lung Cancers Chemoprevention And Therapy, Shaoyi Huang

Dissertations & Theses (Open Access)

Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Despite improvement in treatment strategies, the 5-year survival rate of lung cancer patients remains low. Thus, effective chemoprevention and treatment approaches are sorely needed. Mutations and activation of KRAS occur frequently in tobacco users and the early stage of development of non-small cell lung cancers (NSCLC). So they are thought to be the primary driver for lung carcinogenesis. My work showed that KRAS mutations and activations modulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors by up-regulating death receptors and …

Protection Of Dietary Polyphenols Against Oral Cancer, Yijian Ding, Hua Yao, Yanan Yao, Leonard Yenwong Fai, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Oral cancer represents a health burden worldwide with approximate 275,000 new cases diagnosed annually. Its poor prognosis is due to local tumor invasion and frequent lymph node metastasis. Better understanding and development of novel treatments and chemo-preventive approaches for the preventive and therapeutic intervention of this type of cancer are necessary. Recent development of dietary polyphenols as cancer preventives and therapeutic agents is of great interest due to their antioxidant and anti-carcinogenic activities. Polyphenols may inhibit carcinogenesis in the stage of initiation, promotion, or progression. In particular, dietary polyphenols decrease incidence of carcinomas and exert protection against oral cancer by …

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 …

Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …

Sulforaphane Inhibits Growth Of Human Breast Cancer Cells And Augments The Therapeutic Index Of The Chemotherapeutic Drug, Gemcitabine, Arif Hussain, Javeria Mohsin, Sathyen Alwin Prabhu, Salema Begum, Qurrat El Ain Nusri, Geetganga Harish, Elham Javed, Munawwar Ali Khan, Chhavi Sharma

All Works

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 …

Interest In Breast Cancer Chemoprevention Among Older Women, Jennifer Tjia, Ellyn Micco, Katrina Armstrong

Jennifer Tjia

OBJECTIVES: The study aim is to describe interest in breast cancer chemoprevention among older women without a history of breast cancer and to determine whether aging-related factors such as diminished life expectancy, increasing comorbidity and medication burden attenuate chemoprevention interest. DESIGN: Cross-sectional survey. SETTING: University of Pennsylvania Health System. PARTICIPANTS: Four-hundred fifty-seven community-dwelling women aged 60-65 years old who were potentially eligible for breast cancer chemoprevention according to guidelines linking risk and eligibility to age. MEASUREMENTS: Interest in breast cancer chemopre vention, Gail model breast cancer risk, perceived breast cancer risk, breast cancer worry, self-reported health status and comorbidities, and …

Oncolog Volume 55, Number 04-05, April-May 2010, John Lebas, Sunni Hoseman

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

• IMAGING NERVES: Tetnus Toxin Offers Promise for Neurography
• INBRIEF: Fight-or-Flight Hormones Linked to Metastasis/Drug Combination Shows Promise for Colon Cancer Chemoprevention
• Compass Spring 2010: Early Uterine Papillary Serous Carcinoma: Treatment Options Tailored to Patient and Disease Characteristcs
• House Call: Addressing the Cosmetic Effects of Breast Cancer

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

All ETDs from UAB

Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …

Oncolog Volume 54, Number 05, May 2009, John Lebas

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

• Targeting Inflammation in Cancer Prevention
• Treating Radiation Necrosis of the Brain
• Preclinical Studies Reveal Effectiveness of Therapies for Pediatric Cancers
• House Call: Protect and Check Your Skin

Structure-Activity Relationship And Mechanistic Studies On The Chemopreventive Activity Of Dipyridamole And Its Analogues, Ja’Wanda Shavon Grant

Theses and Dissertations (ETD)

There is an escalating demand in the area of cancer prevention and control for the development of novel agents and molecular targets that have potential to reduce the incidence of cancer. In this study, the JB6 mouse epidermal cell-culture based transformation model was used in efforts to identify novel chemopreventive agents and targets. The nucleoside transport inhibitor dipyridamole (DPM) showed potent chemopreventive activity against JB6 P⁺cells (tumor promotion sensitive). To probe the effects of DPM structural features on its antitumor promotion activity, the soft-agar colony forming efficiency assay was used to screen an in-house library of …

Seaweed And Soy: Companion Foods In Asian Cuisine And Their Effects On Thyroid Function In American Women, Jane Teas, Lewis E. Braverman, Mindy S. Kurzer, Sam Pino, Thomas G. Hurley, James R. Hébert

Faculty Publications

Seaweeds and soy are two commonly eaten foods in Asia. Both have been reported to affect thyroid function, seaweed because of its iodine content and soy because of its goitrogenic effect. Twenty-five healthy postmenopausal women (mean age 58 years) completed a double-blinded randomized crossover study. Ten capsules (5 g/day) of placebo or seaweed (Alaria exculenta), providing 475 ug of iodine/day, were consumed daily for 7 weeks. A powdered soy protein isolate (Solae Co., St. Louis, MO) providing 2 mg of isoflavones/kg of body weight, was given daily during the last week of each treatment arm. On average, …

Oncolog, Volume 52, Number 10, October 2007, Diane Witter, Vickie J. Williams, Michael Fisch Md, Mph

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

• Cancer Chemoprevention: A Prescription for Health?
• Clinic Targets Oral Cancer at Early Stages
• Customized Cancer Care for Kids
• Hotline Consultation Available for Suspected Cancer Cases
• House Call: Cancer Stages: Understanding the Basics
• DiaLog: Rethinking the Standard of Care, by Michael Fisch, MD, MPH

Chemoprevention Of Breast Cancer For Women At Hgh Risk, Kathryn Chan, Gloria J. Morris

Department of Medicine Faculty Papers

Breast cancer remains the second most common cause of cancer death in the United States. Several studies have identified cohorts of women at higher than average risk to develop this disease. These are women who are exposed to high levels of endogenous or exogenous estrogens, those with a family history of breast cancer, and those who harbor benign breast disease or genetic mutations that predispose to breast cancer. In this population group, adapting a chemoprevention strategy to decrease the risk of developing overt disease is a strong consideration. To this end, tamoxifen is the most accepted agent to date. This …

Oncolog, Volume 50, Number 07/08, July-August 2005, Rachel Williams, Sunni Hosemann

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

• Getting Proactive About Prevention
• New Techniques in Tumor Ablation
• House Call: Calling for Help: Cancer Helplines and What They Offer

Oncolog, Volume 49, Number 12, December 2004, David Galloway, Katie Prout Matias, Diane Witter, Paul Mathew Md

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

• Advances in Prostate Cancer Treatment
• Everyday Drugs Show New Promise for Cancer
• Are COX-2 Inhibitors Safe?
• House Call: Myths & Facts about Cancer Prevention
• DiaLog: Neoadjuvant Trials in Prostate Cancer, by Paul Mathew, MD, Assistant Professor, Department of Genitourinary Medical Oncology

Oncolog, Volume 49, Number 02, February 2004, Sunni Hosemann, Aurelio Matamoros

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

• Colorectal Cancer Screening: Encouraging Compliance Today and Looking to the Future
• Despite Its Drawbacks, Mammography Is Still Recommended
• Communication Is Essential When Guiding Patients through the Maze of Genetic Breast Cancer Screening
• House Call: Cancer Epidemiology, Step-by-Step
• DiaLog: On Being a Volunteer, by Anderson Network volunteer

Oncolog, Volume 48, Number 04, April 2003, Katie Prout Matias, Karen Stuyck

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

• Study of Epigenetic Changes Leads to Treatment Advances in Adult Leukemias
• Protocols: Studies Examine Treatment of Leukemia
• The Cost of Caring: Dealing with the Stress of Being an Oncologist
• Excerpts from Focus Groups Featured in Video to Help Oncologists Cope with Stress
• House Call: Chemoprevention: Preventing Cancer with a Pill

Oncolog, Volume 47, Number 04, April 2002, Beth Notzon, Karen Stuyck, Felipe Samaniego Md

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

• Researchers Focus on Bioimmunotherap for Treatment of Non-Hodgkin's Lymphomas
• Protocols: Non-Hodgkin's Lymphoma Studies
• House Call: The First Cancer Prevention Vaccine
• DiaLog: The Viral Origins of Lymphomas, by Felipe Samaniego, MD, Assistant Professor, Department of Lymphoma and Myeloma
• Research Consortium Recruiting Volunteers to Study the Role of Genetics in Cancer Development and Patient Care