Obstetrics and Gynecology Commons^™

Pertussis And Influenza Immunization: Perceived Attitude And Decision Of Postpartum Patients, Nutan B Hebballi, Tayler Parker, Elisa I Garcia, Dalya M Ferguson, Susan Lesser, Kuojen Tsao, Maryam Broussard, Susan H Wootton

Faculty, Staff and Student Publications

BACKGROUND: Vaccination of pregnant patients with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccine during influenza season can reduce maternal and fetal morbidity and mortality; nevertheless, vaccination rates remain suboptimal in this patient population. To investigate the effect of a brief educational counseling session on maternal Tdap and influenza vaccination and determine factors influencing women's decision in regards to receiving Tdap and or influenza vaccine during their pregnancy.

METHODS: A face-to-face semi-structured cross-sectional survey was administered to postpartum patients on their anticipated day of discharge (June 11-August 21, 2018). A brief educational counseling session about maternal …

The Maternal And Infant Environmental Health Riskscape Study Of Perinatal Disparities In Greater Houston: Rationale, Study Design And Participant Profiles, R Jeanne Ruiz, Kristyn Grimes, Elizabeth Spurlock, Angela Stotts, Thomas F Northrup, Yolanda Villarreal, Robert Suchting, Melissa Cernuch, Liza Rivera, Raymond P Stowe, Rita H Pickler

Faculty, Staff and Student Publications

BACKGROUND: Pregnant Mexican Americans (hereafter called Latinas) and Black/African American women are at increased risk for psychological distress, contributing to preterm birth and low birthweight; acculturative stress combined with perceived stress elevates depressive symptoms in Latinas. Based on our prior research using a psychoneuroimmunology framework, we identified psychological and neuroendocrine risk factors as predictors of preterm birth in Latina women that are also identified as risk factors for Black/African American women.

METHODS/DESIGN: In this prospective, randomized controlled trial with parallel group design we will explore psychosocial, neuroendocrine, and birth outcome effects of the Mastery Lifestyle Intervention (MLI). The MLI is …

Molecular Markers In Maternal Blood Exosomes Allow Early Detection Of Fetal Alcohol Spectrum Disorders, Nune Darbinian, Armine Darbinyan, John Sinard, Gabriel Tatevosian, Nana Merabova, Faith D'Amico, Tarek Khader, Ahsun Bajwa, Diana Martirosyan, Alina K Gawlinski, Richa Pursnani, Huaqing Zhao, Shohreh Amini, Mary Morrison, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Prenatal alcohol exposure can cause developmental abnormalities (fetal alcohol spectrum disorders; FASD), including small eyes, face and brain, and neurobehavioral deficits. These cannot be detected early in pregnancy with available imaging techniques. Early diagnosis could facilitate development of therapeutic interventions. Banked human fetal brains and eyes at 9−22 weeks’ gestation were paired with maternal blood samples, analyzed for morphometry, protein, and RNA expression, and apoptotic signaling. Alcohol (EtOH)-exposed (maternal self-report) fetuses were compared with unexposed controls matched for fetal age, sex, and maternal race. Fetal brain-derived exosomes (FB-E) were isolated from maternal blood and analyzed for protein, RNA, and apoptotic …

Targeting Tmem205 Mediated Drug Resistance In Ovarian Clear Cell Carcinoma Using Oncolytic Virus, Uksha Saini, Brentley Q Smith, Kalpana Deepa Priya Dorayappan, Ji Young Yoo, G Larry Maxwell, Balveen Kaur, Ikuo Konishi, David O'Malley, David E Cohn, Karuppaiyah Selvendiran

Faculty, Staff and Student Publications

BACKGROUND: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment challenges and the overall prognosis is far worse than high grade serous ovarian cancer HGSOC. The objective of this study was to examine the therapeutic relevance of combining oncolytic virus with cisplatin for ovarian cancer clear cell carcinoma (OCCC).

RESULTS: We identified that TMEM205, a recently discovered transmembrane protein, contributes to chemoresistance in OCCC cells via the exosomal pathway. Mechanistically, TMEM205 undergoes ligand-independent constitutive endocytosis and co-localizes with Rab11 to contribute to the …

The Integrative Conjugative Element Icespym92 Contributes To Pathogenicity Of Emergent Antimicrobial-Resistant Emm92 Group A Streptococcus, Ji-Sun Lee, Michael W Lero, Jose Mercado-Matos, Sha Zhu, Minjeong Jo, Claire E Tocheny, Jennifer S Morgan, Leslie M Shaw

Faculty, Staff and Student Publications

Despite the strong association of the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway with tumor initiation, recurrence, and metastasis, the mechanism by which this pathway regulates cancer progression is not well understood. Here, we report that IIS supports breast cancer stem cell (CSC) self-renewal in an IRS2-phosphatidylinositol 3-kinase (PI3K)-dependent manner that involves the activation and stabilization of MYC. IRS2-PI3K signaling enhances MYC expression through the inhibition of GSK3β activity and suppression of MYC phosphorylation on threonine 58, thus reducing proteasome-mediated degradation of MYC and sustaining active pS62-MYC function. A stable T58A-Myc mutant rescues CSC function in Irs2−/− cells, supporting …

Community Access To Primary Care Is An Important Geographic Disparity Among Ovarian Cancer Patients Undergoing Cytoreductive Surgery, Abigail S Zamorano, Angela L Mazul, Christine Marx, Mary M Mullen, Molly Greenwade, L Stewart Massad, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, Katherine C Fuh, Matthew A Powell, David G Mutch, Dineo Khabele, Lindsay M Kuroki

Faculty, Staff and Student Publications

OBJECTIVE: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients.

METHODS: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses …

An Optimized Cell-Based Assay To Assess Influenza Virus Replication By Measuring Neuraminidase Activity And Its Applications For Virological Surveillance, Mira C Patel, Daniel Flanigan, Chenchen Feng, Anton Chesnokov, Ha T Nguyen, Anwar Abd Elal, John Steel, Rebecca J Kondor, David E Wentworth, Larisa V Gubareva, Vasiliy P Mishin

Faculty, Staff and Student Publications

Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of …

Targeting The Mtor Pathway For The Prevention Of Er-Negative Breast Cancer, Abhijit Mazumdar, William M Tahaney, Jamal L Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, Jing Qian, Alejandro Contreras, Michelle I Savage, Lana A Vornik, Shizuko Sei, Altaf Mohammed, Powel H Brown

Faculty, Staff and Student Publications

Our results show that everolimus delays mammary tumor formation in multiple mouse models, suggesting that mTOR inhibitors will be useful for the prevention of ER-negative and triple-negative breast cancer in humans. See related Spotlight, p. 787.

Adjuvant Therapy In Women With Early Stage Uterine Serous Carcinoma: A Multi-Institutional Study, Katherine C Kurnit, Silvana Pedra Nobre, Bryan M Fellman, David A Iglesias, Kristina Lindemann, Anuja Jhingran, Ane Gerda Z Eriksson, Beyhan Ataseven, Gretchen E Glaser, Jennifer J Mueller, Shannon N Westin, Pamela T Soliman

Faculty, Staff and Student Publications

OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma.

METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall …

Safety And Efficacy Of Hsp90 Inhibitor Ganetespib For Neoadjuvant Treatment Of Stage Ii/Iii Breast Cancer, Julie E Lang, Andres Forero-Torres, Douglas Yee, Christina Yau, Denise Wolf, John Park, Barbara A Parker, A Jo Chien, Anne M Wallace, Rashmi Murthy, Kathy S Albain, Erin D Ellis, Heather Beckwith, Barbara B Haley, Anthony D Elias, Judy C Boughey, Rachel L Yung, Claudine Isaacs, Amy S Clark, Hyo S Han, Rita Nanda, Qamar J Khan, Kristen K Edmiston, Erica Stringer-Reasor, Elissa Price, Bonnie Joe, Minetta C Liu, Lamorna Brown-Swigart, Emanuel F Petricoin, Julia D Wulfkuhle, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Adam L Asare, Jeffrey B Matthews, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van 'T Veer, Nola M Hylton, Angela M Demichele, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to …

Cell-Free Dna Screening Positive For Monosomy X: Clinical Evaluation And Management Of Suspected Maternal Or Fetal Turner Syndrome, Tazim Dowlut-Mcelroy, Shanlee Davis, Susan Howell, Iris Gutmark-Little, Vaneeta Bamba, Siddharth Prakash, Sheetal Patel, Doris Fadoju, Nandini Vijayakanthi, Mary Haag, Deborrah Hennerich, Lorraine Dugoff, Roopa Kanakatti Shankar

Faculty, Staff and Student Publications

Initially provided as an alternative to evaluation of serum analytes and nuchal translucency for the assessment of pregnancies at high risk of trisomy 21, cell-free DNA screening for fetal aneuploidy, also referred to as noninvasive prenatal screening, can now also screen for fetal sex chromosome anomalies such as monosomy X as early as 9 to 10 weeks of gestation. Early identification of Turner syndrome, a sex chromosome anomaly resulting from the complete or partial absence of the second X chromosome, allows medical interventions such as optimizing obstetrical outcomes, hormone replacement therapy, fertility preservation and support, and improved neurocognitive outcomes. However, …

Inclusion Of Premenopausal Women In Breast Cancer Clinical Trials, Kelsey L Corrigan, Ramez Kouzy, Joseph Abi Jaoude, Roshal R Patel, Rachel M Layman, Sharon H Giordano, Wendy A Woodward, Benjamin D Smith, Simona F Shaitelman, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.

METHODS: Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.

RESULTS: Of 170 breast …

Obstetric And Neonatal Outcomes 1 Or More Years After A Diagnosis Of Breast Cancer, Kirsten Jorgensen, Roni Nitecki, Hazel B Nichols, Shuangshuang Fu, Chi-Fang Wu, Alexander Melamed, Paula Brady, Mariana Chavez Mac Gregor, Mark A Clapp, Sharon Giordano, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.

METHODS: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December …

An Ai-Driven Clinical Care Pathway To Reduce 30-Day Readmission For Chronic Obstructive Pulmonary Disease (Copd) Patients, Lin Wang, Guihua Li, Chika F Ezeana, Richard Ogunti, Mamta Puppala, Tiancheng He, Xiaohui Yu, Solomon S Y Wong, Zheng Yin, Aaron W Roberts, Aryan Nezamabadi, Pingyi Xu, Adaani Frost, Robert E Jackson, Stephen T C Wong

Faculty, Staff and Student Publications

Healthcare regulatory agencies have mandated a reduction in 30-day hospital readmission rates and have targeted COPD as a major contributor to 30-day readmissions. We aimed to develop and validate a simple tool deploying an artificial neural network (ANN) for early identification of COPD patients with high readmission risk. Using COPD patient data from eight hospitals within a large urban hospital system, four variables were identified, weighted and validated. These included the number of in-patient admissions in the previous 6 months, the number of medications administered on the first day, insurance status, and the Rothman Index on hospital day one. An …

Racial And Ethnic Disparities In Primary Cesarean Birth And Adverse Outcomes Among Low-Risk Nulliparous People, Michal Fishel Bartal, Han-Yang Chen, Hector Mendez-Figueroa, Stephen M Wagner, Suneet S P Chauhan

Faculty, Staff and Student Publications

Objective: To compare trend of primary cesarean delivery rate and composite neonatal and maternal adverse outcomes in low-risk pregnancies among racial and ethnic groups: non-Hispanic White, non-Hispanic Black, and Hispanic.

Methods: This population-based cohort study used U.S. vital statistics data (2015-2019) to evaluate low-risk, nulliparous patients with nonanomalous singletons who labored and delivered at 37-41 weeks of gestation. The primary outcome was the primary cesarean delivery rate. Secondary outcomes included composite neonatal adverse outcome (Apgar score less than 5 at 5 minutes, assisted ventilation for more than 6 hours, seizure, or death), and composite maternal adverse outcome (intensive care unit …

Outcomes Of Gynecologic Cancer Surgery During The Covid-19 Pandemic: An International, Multicenter, Prospective Covidsurg-Gynecologic Oncology Cancer Study, Christina Fotopoulou, Tabassum Khan, Juraj Bracinik, James Glasbey, Nadeem Abu-Rustum, Luis Chiva, Anna Fagotti, Keiichi Fujiwara, Rahel Ghebre, Murat Gutelkin, Thomas O Konney, Joseph Ng, Rene Pareja, Rajkumar Kottayasamy Seenivasagam, Jalid Sehouli, Shylasree T S Surappa, Aneel Bhangu, Elaine Leung, Sudha Sundar

Faculty, Staff and Student Publications

BACKGROUND: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear.

OBJECTIVE: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive …

The Reading Profiles Of Late Elementary English Learners With And Without Dyslexia, Pia Tohme, Rudy Abi-Habib, Elma Nassar, Nouran Hamed, Gaël Abou-Ghannam, Gihad E Chalouhi

Faculty, Staff and Student Publications

This study aimed to assess the impact of the COVID-19 stress and anxiety on prenatal attachment during the second trimester of gestation. Pregnancy is an important stage for mothers-to-be in creating representations of themselves as a "mother", with the developing attachment relationship to the unborn child considered as a milestone in the future parent's developmental trajectory. The outbreak of the COVID-19 pandemic and the national health measures installed can hence have consequences on these representations and on prenatal attachment. Our sample consisted of 95 mothers that were recruited from a prenatal ultrasound screening center. Results suggested that the COVID-19 pandemic …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Meng Lin, Amy T Ku, Jie Dong, Fei Yue, Weiyu Jiang, Ahmed Atef Ibrahim, Fanglue Peng, Chad J Creighton, Chandandeep Nagi, Carolina Gutierrez, Jeffrey M Rosen, Xiang H-F Zhang, Susan G Hilsenbeck, Xi Chen, Yi-Chieh Nancy Du, Shixia Huang, Aiping Shi, Zhimin Fan, Yi Li

Faculty, Staff and Student Publications

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in …

Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha

Faculty, Staff and Student Publications

OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.

METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build …

Lessons From The Failure To Complete A Trial Of Denosumab In Women With A Pathogenic Brca1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy, Meghna S Trivedi, Nadir Arber, Eitan Friedman, Judy E Garber, Kevin Holcomb, Neil S Horowitz, Jason D Wright, J Jack Lee, Lana A Vornik, Saba Abutaseh, Tawana Castile, Edward R Sauter, Eileen Dimond, Brandy M Heckman-Stoddard, Margaret House, Goli Samimi, Powel H Brown, Katherine D Crew

Faculty, Staff and Student Publications

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO …

Assessing Urinary Phenol And Paraben Mixtures In Pregnant Women With And Without Gestational Diabetes Mellitus: A Case-Control Study, Wei-Jen Chen, Candace Robledo, Erin M Davis, Jean R Goodman, Chao Xu, Jooyeon Hwang, Amanda E Janitz, Tabitha Garwe, Antonia M Calafat, Jennifer D Peck

Faculty, Staff and Student Publications

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable …

Feasibility Of A Novel Non-Invasive Swab Technique For Serial Whole-Exome Sequencing Of Cervical Tumors During Chemoradiation Therapy, Julianna K Bronk, Chiraag Kapadia, Xiaogang Wu, Bhavana V Chapman, Rui Wang, Tatiana V Karpinets, Xingzhi Song, Andrew M Futreal, Jianhua Zhang, Ann H Klopp, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Clinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to demonstrate the feasibility of a novel noninvasive cervical swab technique to (1) collect tumor DNA with adequate throughput to (2) perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT).

METHODS: Cervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were …

Classification Of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics, Katelyn F Handley, Travis T Sims, Nicholas W Bateman, Deanna Glassman, Katherine I Foster, Sanghoon Lee, Jun Yao, Hui Yao, Bryan M Fellman, Jinsong Liu, Zhen Lu, Kelly A Conrads, Brian L Hood, Waleed Barakat, Li Zhao, Jianhua Zhang, Shannon N Westin, Joseph Celestino, Kelly M Rangel, Sunil Badal, Igor Pereira, Prahlad T Ram, George L Maxwell, Livia S Eberlin, P Andrew Futreal, Robert C Bast, Nicole D Fleming, Thomas P Conrads, Anil K Sood

Faculty, Staff and Student Publications

IMPORTANCE: Despite similar histologic appearance among high-grade serous ovarian cancers (HGSOCs), clinical observations suggest vast differences in gross appearance. There is currently no systematic framework by which to classify HGSOCs according to their gross morphologic characteristics.

OBJECTIVE: To develop and characterize a gross morphologic classification system for HGSOC.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with suspected advanced-stage ovarian cancer who presented between April 1, 2013, and August 5, 2016, to the University of Texas MD Anderson Cancer Center, a large referral center. Patients underwent laparoscopic assessment of disease burden before treatment and received a histopathologic diagnosis of …

Lenvatinib Plus Pembrolizumab In Japanese Patients With Endometrial Cancer: Results From Study 309/Keynote-775, Kan Yonemori, Mayu Yunokawa, Kimio Ushijima, Jun Sakata, Ayumi Shikama, Shinichiro Minobe, Tomoka Usami, Takayuki Enomoto, Kazuhiro Takehara, Kosei Hasegawa, Wataru Yamagami, Keiko Yamamoto, Shirong Han, Lea Dutta, Robert Orlowski, Takuma Miura, Vicky Makker, Keiichi Fujiwara

Faculty, Staff and Student Publications

Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m

Use Of Breast Surveillance Between Women With Pathogenic Variants And Variants Of Uncertain Significance In Breast Cancer Susceptibility Genes, Sukh Makhnoon, Minxing Chen, Brooke Levin, Megan Ensinger, Kristin D Mattie, Generosa Grana, Sanjay Shete, Banu K Arun, Susan K Peterson

Faculty, Staff and Student Publications

BACKGROUND: Use of surveillance mammography and magnetic resonance imaging (MRI) has been understudied among women with variant of uncertain significance (VUS) compared to pathogenic and likely pathogenic variants (P/LP).

METHODS: Using data from two cancer settings, we calculated use of risk-reducing mastectomy (RRM) and surveillance during each 13-month span after genetic testing up to 6 years afterwards for a cohort of genetically elevated risk women.

RESULTS: Of 889 women, VUS carriers were less likely to undergo RRM compared to those with P/LP (hazard ratio [HR], 0.17; p =

CONCLUSION: The authors found that VUS, whether in high or moderate penetrance …

Integration Of Mouse Ovary Morphogenesis With Developmental Dynamics Of The Oviduct, Ovarian Ligaments, And Rete Ovarii, Jennifer Mckey, Dilara N Anbarci, Corey Bunce, Alejandra E Ontiveros, Richard R Behringer, Blanche Capel

Faculty, Staff and Student Publications

Morphogenetic events during the development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii (RO) elaborated into a convoluted tubular structure extending …

Reproductive Health Perspectives Of Young Women With Perinatally And Behaviourally Acquired Hiv: A Qualitative Study, Lizelle Comfort, Dana Watnick, Melissa Peskin, Julie Gutierrez, Jacob Abadi, Jessica Atrio

Faculty, Staff and Student Publications

INTRODUCTION: The aim of this study was to describe the sexual and reproductive goals of female adolescents with human immunodeficiency virus (HIV) in an urban cohort and decipher if they vary depending on the mode of HIV acquisition.

METHODS: We conducted in-depth qualitative interviews with 25 Black and/or Hispanic/Latinx female adolescents living with HIV (14 perinatally, 11 behaviourally acquired) aged 17-25 years who have access to care and antiretroviral therapy at an urban public hospitals (NYC, NY). Interviews were transcribed, coded and analysed using thematic analysis.

RESULTS: Interviews demonstrated that access to antiretroviral therapy and HIV disclosure to a sexual …

Biophysical And Biochemical Characterization Of The Receptor Binding Domain Of Sars-Cov-2 Variants, Ritika Khatri, Hilal Ahmad Parray, Gazala Siddiqui, Adarsh Kumar Chiranjivi, Sneha Raj, Rachel Kaul, Vikas Maithil, Sweety Samal, Shubbir Ahmed

Faculty, Staff and Student Publications

The newly emerging SARS-CoV-2 variants are potential threat and posing new challenges for medical intervention due to high transmissibility and escaping neutralizing antibody (NAb) responses. Many of these variants have mutations in the receptor binding domain (RBD) of SARS-CoV-2 spike protein that interacts with the host cell receptor. Rapid mutation in the RBD through natural selection to improve affinity for host receptor and antibody pressure from vaccinated or infected individual will greatly impact the presently adopted strategies for developing interventions. Understanding the nature of mutations and how they impact the biophysical, biochemical and immunological properties of the RBD will help …

Metagenomes Of Rectal Swabs In Larger, Advanced Stage Cervical Cancers Have Enhanced Mucus Degrading Functionalities And Distinct Taxonomic Structure, Tatiana V Karpinets, Xiaogang Wu, Travis Solley, Molly B El Alam, Travis T Sims, Kyoko Yoshida-Court, Erica Lynn, Mustapha Ahmed-Kaddar, Greyson Biegert, Jingyan Yue, Xingzhi Song, Huandong Sun, Joseph F Petrosino, Melissa P Mezzari, Pablo Okhuysen, Patricia J Eifel, Anuja Jhingran, Lilie L Lin, Kathleen M Schmeler, Lois Ramondetta, Nadim Ajami, Robert R Jenq, Andrew Futreal, Jianhua Zhang, Ann H Klopp, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC.

METHOD: Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics.

RESULTS: Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified …

Poziotinib Inhibits Her2-Mutant-Driven Therapeutic Resistance And Multiorgan Metastasis In Breast Cancer, Rashi Kalra, Ching Hui Chen, Junkai Wang, Ahmad Bin Salam, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Clayton C Yates, Carolina Gutierrez, Balasubramanyam Karanam, Meenakshi Anurag, Bora Lim, Matthew J Ellis, Shyam M Kavuri

Faculty, Staff and Student Publications

The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan …