Digital Commons Network^™

Initial Experiences Using Plasma Rich In Growth Factors To Treat Keratoneuralgia, Margaret Wang, Sowmya Yennam, Stephen Pflugfelder

Faculty, Staff and Students Publications

Keratoneuralgia, a clinical diagnosis of sensitized corneal pain without visible ocular surface damage, generally has minimal response to conventional therapies. Causes include refractive surgery and chronic dry eye. We evaluated the efficacy of Plasma Rich in Growth Factors (PRGF), a novel treatment prepared using a commercially available kit, in patients with keratoneuralgia. A retrospective chart review identified patients who had the clinical diagnosis of keratoneuralgia and were treated with PRGF for at least 3 months from October 2015 to April 2020 at a single academic institution. Both objective eye exam findings and concurrent treatments were obtained at baseline, 3 months, …

Comprehensive Improvement Of Cardiology Inpatient Transfers: A Bed-Availability Triggered Approach, Judson A Moore, Lindsay F Eilers, Amanda J Willis, Michael D Chance, Julie A La Salle, Ellen H Delgado, Katie M Bien, Jordana R Goldman, Shreya S Sheth

Faculty, Staff and Students Publications

INTRODUCTION: Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture.

METHODS: We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and …

Evaluation Of Cervical Spine Pathology In Children With Loeys-Dietz Syndrome, Marc Andrew Prablek, Melissa Lopresti, Brandon Bertot, Shaine Alaine Morris, David Bauer, Sandi Lam, Vijay Ravindra

Faculty, Staff and Students Publications

BACKGROUND: Loeys-Dietz syndrome (LDS) is a genetic connective tissue disorder associated with multiple musculoskeletal anomalies, including cervical spine instability. We sought to examine the nature of imaging for cervical spine instability in children with LDS due to likely pathogenic or pathogenic variants in

METHODS: A retrospective chart review was conducted, examining relevant data for all children with LDS screened at our institution from 2004 through 2021. Cervical spine X-rays were used to assess cervical instability, cervical lordosis, and basilar impression.

RESULTS: A total of 39 patients were identified; 16 underwent cervical spine screening (56.25% male). Median age at initial screening …

The Nhlbi Study On Long-Term Outcomes After The Multisystem Inflammatory Syndrome In Children (Music): Design And Objectives, Dongngan T Truong, Felicia L Trachtenberg, Gail D Pearson, Audrey Dionne, Matthew D Elias, Kevin Friedman, Kerri H Hayes, Lynn Mahony, Brian W Mccrindle, Matthew E Oster, Victoria Pemberton, Andrew J Powell, Mark W Russell, Lara S Shekerdemian, Mary Beth Son, Michael Taylor, Jane W Newburger

Faculty, Staff and Students Publications

BACKGROUND: The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood.

METHODS: This multicenter observational cohort study will enroll at least 600 patientsyears, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF)

CONCLUSION: The MUSIC study, with the largest cohort of MIS-C patients and the longest …

Current State Of The Art In Hypoplastic Left Heart Syndrome, Aditya K Birla, Sunita Brimmer, Walker D Short, Oluyinka O Olutoye, Jason A Shar, Suriya Lalwani, Philippe Sucosky, Anitha Parthiban, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla

Faculty, Staff and Students Publications

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures. With recent advances in surgical management of HLHS patients, high survival rates are now obtained at tertiary treatment centers, though adverse neurodevelopmental outcomes remain a clinical challenge. While surgical management remains the standard of care for …

Artificial Intelligence In The Pediatric Echocardiography Laboratory: Automation, Physiology, And Outcomes, Minh B Nguyen, Olivier Villemain, Mark K Friedberg, Lasse Lovstakken, Craig G Rusin, Luc Mertens

Faculty, Staff and Students Publications

Artificial intelligence (AI) is frequently used in non-medical fields to assist with automation and decision-making. The potential for AI in pediatric cardiology, especially in the echocardiography laboratory, is very high. There are multiple tasks AI is designed to do that could improve the quality, interpretation, and clinical application of echocardiographic data at the level of the sonographer, echocardiographer, and clinician. In this state-of-the-art review, we highlight the pertinent literature on machine learning in echocardiography and discuss its applications in the pediatric echocardiography lab with a focus on automation of the pediatric echocardiogram and the use of echo data to better …

Optimal Fenestration Of The Fontan Circulation, Zan Ahmad, Lynn H Jin, Daniel J Penny, Craig G Rusin, Charles S Peskin, Charles Puelz

Faculty, Staff and Students Publications

In this paper, we develop a pulsatile compartmental model of the Fontan circulation and use it to explore the effects of a fenestration added to this physiology. A fenestration is a shunt between the systemic and pulmonary veins that is added either at the time of Fontan conversion or at a later time for the treatment of complications. This shunt increases cardiac output and decreases systemic venous pressure. However, these hemodynamic benefits are achieved at the expense of a decrease in the arterial oxygen saturation. The model developed in this paper incorporates fenestration size as a parameter and describes both …

Obesity And Asthma: A Focused Review, Rubabin Tooba, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

Dual Orexin Receptor Antagonists For Treatment Of Insomnia: A Systematic Review And Meta-Analysis On Randomized, Double-Blind, Placebo-Controlled Trials Of Suvorexant And Lemborexant, Habibolah Khazaie, Masoud Sadeghi, Sepideh Khazaie, Max Hirshkowitz, Amir Sharafkhaneh

Faculty, Staff and Students Publications

Study objectives: Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.

Methods: We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval …

An Exploratory Assessment Of The Management Of Pediatric Traumatic Brain Injury In Three Centers In Africa, Madiha Raees, Shubhada Hooli, Amélie O Von Saint André-Von Arnim, Tsegazeab Laeke, Easmon Otupiri, Anthony Fabio, Kristina E Rudd, Rashmi Kumar, Patrick T Wilson, Abenezer Tirsit Aklilu, Lisine Tuyisenge, Chunyan Wang, Robert C Tasker, Derek C Angus, Patrick M Kochanek, Ericka L Fink, Tigist Bacha

Faculty, Staff and Students Publications

PURPOSE: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). Hospital care practices of pediatric TBI patients in LMICs are unknown. Our objective was to report on hospital management and outcomes of children with TBI in three centers in LMICs.

METHODS: We completed a secondary analysis of a prospective observational study in children (<18 >years) over a 4-week period. Outcome was determined by Pediatric Cerebral Performance Category (PCPC) score; an unfavorable score was defined as PCPC > 2 or an increase of two points from baseline. Data were compared using Chi-square and …

The Burden Of Critical Illness In Hospitalized Children In Low- And Middle-Income Countries: Protocol For A Systematic Review And Meta-Analysis, Teresa B Kortz, Katie R Nielsen, Rishi P Mediratta, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Jonah E Attebery, Emaan G Bhutta, Carter Biewen, Alvaro Coronado Munoz, Mary L Dealmeida, Yudy Fonseca, Shubhada Hooli, Hunter Johnson, Niranjan Kissoon, Mara L Leimanis-Laurens, Amanda M Mccarthy, Carol Pineda, Kenneth E Remy, Sara C Sanders, Yemisi Takwoingi, Matthew O Wiens, Adnan T Bhutta

Faculty, Staff and Students Publications

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.

DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 …

Why Test Results Are Still Getting "Lost" To Follow-Up: A Qualitative Study Of Implementation Gaps, Andrew J Zimolzak, Umber Shahid, Traber D Giardina, Sahar A Memon, Umair Mushtaq, Lisa Zubkoff, Daniel R Murphy, Andrea Bradford, Hardeep Singh

Faculty, Staff and Students Publications

BACKGROUND: Lack of timely follow-up of abnormal test results is common and has been implicated in missed or delayed diagnosis, resulting in potential for patient harm.

OBJECTIVE: As part of a larger project to implement change strategies to improve follow-up of diagnostic test results, this study sought to identify specifically where implementation gaps exist, as well as possible solutions identified by front-line staff.

DESIGN: We used a semi-structured interview guide to collect qualitative data from Veterans Affairs (VA) facility staff who had experience with test results management and patient safety.

SETTING: Twelve VA facilities across the USA.

PARTICIPANTS: Facility staff …

Fourteen-Day Vonoprazan And Low- Or High-Dose Amoxicillin Dual Therapy For Eradicating Helicobacter Pylori Infection: A Prospective, Open-Labeled, Randomized Non-Inferiority Clinical Study, Yi Hu, Xin Xu, Xiao-Shun Liu, Cong He, Yao-Bin Ouyang, Nian-Shuang Li, Chuan Xie, Chao Peng, Zhen-Hua Zhu, Yong Xie, Xu Shu, Yin Zhu, David Y Graham, Nong-Hua Lu

Faculty, Staff and Students Publications

BACKGROUND AND AIM: We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for

METHODS: This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve

RESULTS: A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups.

CONCLUSION: VPZ with b.i.d. …

Depression And Anxiety Are Common Among Patients With Cirrhosis, Ruben Hernaez, Jennifer R Kramer, Aisha Khan, Jessica Phillips, Katharine Mccallister, Kassie Chaffin, Adriana Portela Hernandez, Hannah Fullington, Cynthia Ortiz, James-Michael Blackwell, Adam Loewen, Yan Liu, Jasmin A Tiro, Simon C Lee, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Depression and anxiety can have negative effects on patients and are important to treat. There have been few studies of their prevalence among patients with cirrhosis. We aimed to characterize the prevalence and risk factors for depression and anxiety in a large multi-center cohort of patients with cirrhosis.

METHODS: We conducted a telephone-based survey of patients with cirrhosis at 3 health systems in the United States (a tertiary-care referral center, a safety net system, and a Veterans hospital) from April through December 2018. Of 2871 patients approached, 1021 (35.6%) completed the survey. Depression and anxiety were assessed …

Associations Of Duration, Intensity, And Quantity Of Smoking With Risk Of Gastric Intestinal Metaplasia, Aaron P Thrift, Andre G Jove, Yan Liu, Mimi C Tan, Hashem B El-Serag

Faculty, Staff and Students Publications

GOAL: Determine whether various dimensions of smoking increase risk for gastric intestinal metaplasia.

BACKGROUND: Cigarette smoking has been implicated in the etiology of gastric cancer, but it is not clear if smoking is a risk factor for gastric intestinal metaplasia, a precursor lesion of gastric cancer.

MATERIALS AND METHODS: We compared data from 385 gastric intestinal metaplasia cases and 1577 controls without gastric intestinal metaplasia recruited into a cross-sectional study at the Michael E. DeBakey VA Medical Center in Houston, Texas. All participants completed standardized questionnaires and underwent a study endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included …

Severe Inflammatory Colitis Related To Encorafenib And Binimetinib Following Immune Checkpoint Inhibitor Therapy, Aaron G Issac, David Szafron, Dongguang Wei, Jennifer L Mcquade, Yinghong Wang

Faculty, Staff and Students Publications

Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic patterns of predominant right colon ulcerations. It can lead to significant morbidity and frequent interruption of cancer treatment. Early recognition and prompt intervention are critical to improving patient outcomes.

Cytomegalovirus Infection Among Patients With Cancer Receiving Immune Checkpoint Inhibitors, Kavea Panneerselvam, David Szafron, Rajan N Amin, Dongguang Wei, Dongfeng Tan, Mehmet Altan, Pablo C Okhuysen, Malek Shatila, Gottumukkala Subba Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Students Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.

METHODS: We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records. …

Inpatient Coding System And Opportunities For Documentation Optimization: An Interactive Session For Internal Medicine Residents, Lindsey Jordan Gay, Doris Lin, Ziba Colah, Glynda Raynaldo

Faculty, Staff and Students Publications

INTRODUCTION: The Inpatient Prospective Payment System, the framework for categorization of admissions, is based upon physician documentation leading to International Classification of Diseases, Tenth Revision code generation and Medical Severity Diagnosis-Related Group (MS-DRG) assignment. In this curriculum, we introduced internal medicine residents to this inpatient coding framework and its effects on hospital quality metrics and reimbursement. We focused on educating learners about the importance of physicians being proficient in providing thorough and specific clinical documentation to produce appropriate DRG assignment.

METHODS: Internal medicine residents participated in a 90-minute session that introduced the basic framework of inpatient coding, discussed effects of …

An Evidence-Based, Structured, Expert Approach To Selecting Essential Indicators Of Primary Care Quality, Sylvia J Hysong, Kelley Arredondo, Ashley M Hughes, Houston F Lester, Frederick L Oswald, Laura A Petersen, Lechauncy Woodard, Edward Post, Shelly Deperalta, Daniel R Murphy, Jason Mcknight, Karin Nelson, Paul Haidet

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this article is to illustrate the application of an evidence-based, structured performance measurement methodology to identify, prioritize, and (when appropriate) generate new measures of health care quality, using primary care as a case example. Primary health care is central to the health care system and health of the American public; thus, ensuring high quality is essential. Due to its complexity, ensuring high-quality primary care requires measurement frameworks that can assess the quality of the infrastructure, workforce configurations, and processes available. This paper describes the use of the Productivity Measurement and Enhancement System (ProMES) to compile a …

Diagnosis And Interpretation Of Testing For Cat Scratch Disease, Nasim Khalfe, Doris Lin

Faculty, Staff and Students Publications

Cat scratch disease (CSD) is an infectious disease caused by Bartonella henselae that presents as regional lymphadenopathy which can appear within weeks after a cat scratch. There is no gold standard for diagnosis. Rather, clinicians rely on an amalgam of criteria to make a definitive diagnosis. We describe a case of a 44-year-old woman with six cats who presented with a painful left inguinal mass, had splenic lesions on imaging, and had positive serology but a negative polymerase chain reaction test for B. henselae.

Multi-Antigen-Targeted T-Cell Therapy To Treat Patients With Relapsed/Refractory Breast Cancer, Valentina Hoyos, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Ifigeneia Tzannou, Yovana Velazquez, Matthew French-Kim, Wingchi Leung, Suhasini Lulla, Catherine Robertson, Claudette Foreman, Tao Wang, Shaun Bulsara, Natalia Lapteva, Bambi Grilley, Matthew Ellis, Charles Kent Osborne, Angela Coscio, Julie Nangia, Helen E Heslop, Cliona M Rooney, Juan F Vera, Premal Lulla, Mothaffar Rimawi, Ann M Leen

Faculty, Staff and Students Publications

PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.

MATERIALS AND METHODS: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 …

Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston

Faculty, Staff and Students Publications

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER

EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.

RESULTS: Higher baselines …

An Unusual Case Of Breast Implant-Associated Anaplastic Large Cell Lymphoma, Sarah Premji, Andreia Barbieri, Christine Roth, Eric M Rohren, Gustavo Rivero, Sravanti P Teegavarapu

Faculty, Staff and Students Publications

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare disease entity associated with textured breast implants. Though the clinical course is typically indolent, BIA-ALCL can occasionally invade through the capsule into the breast parenchyma with spread to the regional lymph nodes and beyond including chest wall invasive disease.

CASE: We present the case of a 51-year-old female with a history of bilateral silicone breast implants placed approximately twenty years ago who presented with two months of progressively enlarging right breast mass. Ultrasound-guided biopsy of right breast mass and right axillary lymph node showed CD 30-positive

CONCLUSION: Treatment guidelines …

The Effects Of Glucocorticoids And Immunosuppressants On Cancer Outcomes In Checkpoint Inhibitor Therapy, Sebastian Bruera, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, …

Hypermethylation Of Pi3k-Akt Signalling Pathway Genes Is Associated With Human Neural Tube Defects, Tian Tian, Xinyuan Lai, Kuanhui Xiang, Xiao Han, Shengju Yin, Robert M Cabrera, John W Steele, Yunping Lei, Xuanye Cao, Richard H Finnell, Linlin Wang, Aiguo Ren

Faculty, Staff and Students Publications

Neural tube defects (NTDs) are a group of common and severe congenital malformations. The PI3K-AKT signalling pathway plays a crucial role in the neural tube development. There is limited evidence concerning any possible association between aberrant methylation in PI3K-AKT signalling pathway genes and NTDs. Therefore, we aimed to investigate potential associations between aberrant methylation of PI3K-AKT pathway genes and NTDs. Methylation studies of PI3K-AKT pathway genes utilizing microarray genome-methylation data derived from neural tissues of ten NTD cases and eight non-malformed controls were performed. Targeted DNA methylation analysis was subsequently performed in an independent cohort of 73 NTD cases and …

Embryonic Hypotaurine Levels Contribute To Strain-Dependent Susceptibility In Mouse Models Of Valproate-Induced Neural Tube Defects, John W Steele, Ying Linda Lin, Nellie Chen, Bogdan J Wlodarczyk, Qiuying Chen, Nabeel Attarwala, Madhu Venkatesalu, Robert M Cabrera, Steven S Gross, Richard H Finnell

Faculty, Staff and Students Publications

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address …

Endometriosis-Associated Angiogenesis And Anti-Angiogenic Therapy For Endometriosis, Monica S Chung, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.

Common Genomic Aberrations In Mouse And Human Breast Cancers With Concurrent P53 Deficiency And Activated Pten-Pi3k-Akt Pathway, Jarrod D Martinez, Qianxing Mo, Yixiang Xu, Li Qin, Yi Li, Jianming Xu

Faculty, Staff and Students Publications

Simultaneous P53 loss and activation of the PTEN-restricted PI3K-AKT pathway frequently occur in aggressive breast cancers. P53 loss causes genome instability, while PTEN loss and/or activating mutations of PIK3CA and AKT promote cancer cell proliferation that also increases incidences of genomic aberrations. However, the genomic alterations associated with P53 loss and activated PTEN-PI3K-AKT signaling in breast cancer have not been defined. Spatiotemporally controlled breast cancer models with inactivation of both P53 and Pten in adult mice have not been established for studying genomic alterations. Herein, we deleted both floxed Pten and Tp53 genes in the mammary gland epithelial cells in …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …

Decidualization Of Human Endometrial Stromal Cells Requires Steroid Receptor Coactivator-3, Vineet K Maurya, Maria M Szwarc, David M Lonard, William E Gibbons, San-Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Steroid receptor coactivator-3 (SRC-3; also known as NCOA3 or AIB1) is a member of the multifunctional p160/SRC family of coactivators, which also includes SRC-1 and SRC-2. Clinical and cell-based studies as well as investigations on mice have demonstrated pivotal roles for each SRC in numerous physiological and pathophysiological contexts, underscoring their functional pleiotropy. We previously demonstrated the critical involvement of SRC-2 in murine embryo implantation as well as in human endometrial stromal cell (HESC) decidualization, a cellular transformation process required for trophoblast invasion and ultimately placentation. We show here that, like SRC-2, SRC-3 is expressed in the epithelial and stromal …