Medicine and Health Sciences Commons^™

Cross-Sectional Analysis Of Primary Care Clinics' Policies, Practices, And Availability Of Patient Support Services During The Covid-19 Pandemic, Kendra Ratnapradipa, Runqiu Wang, Josiane Kabayundo, Walter Marquez Lavenant, Eleanore Nelson, Muskan Ahuja, Ying Zhang, Hongmei Wang

Journal Articles: Epidemiology

BACKGROUND: Healthcare accessibility and utilization are important social determinants of health. Lack of access to healthcare, including missed or no-show appointments, can have negative health effects and be costly to patients and providers. Various office-based approaches and community partnerships can address patient access barriers.

OBJECTIVES: (1) To understand provider perceptions of patient barriers; (2) to describe the policies and practices used to address late or missed appointments, and (3) to evaluate access to patient support services, both in-clinic and with community partners.

METHODS: Mailed cross-sectional survey with online response option, sent to all Nebraska primary care clinics (n = 577) …

Exploring The Dynamics Of Attracting And Retaining Acute Care Psychiatric Registered Nurses: An In-Depth Analysis Using Focus Groups, Kendra Ratnapradipa, Julia F. Houfek, Phoebe Gearhart, Erin O. Scheider, Christine Chasek, Danae Dinkel, Katrina M. Cordts, Marley Doyle, Priyanka Chaudhary, Deepanjali Bhale, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

The recruitment and retention of in-patient psychiatric mental health registered nurses (PMH-RNs) remains a challenge. This qualitative study sought to identify factors impacting the recruitment and retention of PMH-RNs in acute-care settings. Participants (N = 15) were recruited for focus groups including one with in-patient unit administrators (n = 4), two with current PMH-RNs (n = 7), and two with nursing students (n = 4). Data were analyzed using a directed content analysis approach. Participants were informed about the study’s purpose, procedures, potential risks, and benefits, and they provided verbal consent before participating. Administrators emphasized a …

Evaluating The Performance Of Flukecatcher At Detecting Urogenital Schistosomiasis, Louis Fok, Berhanu Erko, David Brett-Major, Abebe Animut, M. Jana Broadhurst, Daisy Dai, John Linville, Bruno Levecke, Yohannes Negash, Abraham Degarege

Journal Articles: Epidemiology

Urine filtration microscopy (UFM) lacks sensitivity in detecting low-intensity Schistosoma haematobium infections. In pursuit of a superior alternative, this study evaluated the performance of FlukeCatcher microscopy (FCM) at detecting S. haematobium eggs in human urine samples. Urine samples were collected from 572 school-age children in Afar, Ethiopia in July 2023 and examined using UFM and FCM approaches. Using the combined UFM and FCM results as a reference, the sensitivity, negative predictive value, and agreement levels for the two testing methods in detecting S. haematobium eggs in urine samples were calculated. The sensitivity and negative predictive value of detecting S. haematobium …

Methodological Assessment Of A Review Of Knowledge, Attitude And Practice About Human Papilloma Virus Vaccination In India, Abraham Degarege, Purnima Madhivanan

Journal Articles: Epidemiology

A well-conducted review provides quality evidence to inform policy and practice. It is important that the review is as rigorous and as fully reported as possible if the evidence from the review is incorporated into clinical practice. We are writing in response to an article titled, ‘Evidence of Knowledge, Attitude, and Practice Regarding Human Papilloma Virus Vaccination at the Community Level in India: A Systematic Review and Meta-Analysis’ by Pal et al published in Asian Pacific Journal of Cancer Prevention in March 2024. There are some major methodological flaws in the paper that might have biased the conclusions drawn from …

Resilience Of Mental Health Services Amidst Ebola Disease Outbreaks In Africa, Frankline Sevidzem Wirsiy, Nancy B. Tahmo, Lambed Tatah, David Brett-Major

Journal Articles: Epidemiology

INTRODUCTION: Health systems including mental health (MH) systems are resilient if they protect human life and produce better health outcomes for all during disease outbreaks or epidemics like Ebola disease and their aftermaths. We explored the resilience of MH services amidst Ebola disease outbreaks in Africa; specifically, to (i) describe the pre-, during-, and post-Ebola disease outbreak MH systems in African countries that have experienced Ebola disease outbreaks, (ii) determine the prevalence of three high burden MH disorders and how those prevalences interact with Ebola disease outbreaks, and, (iii) describe the resilience of MH systems in the context of these …

Assessing De Novo Parasite Genomes Assembled Using Only Oxford Nanopore Technologies Minion Data, Kaylee Herzog, Rachel Wu, John M. Hawdon, Peter Nejsum, Joseph R. Fauver

Journal Articles: Epidemiology

In this study, we assessed the quality of de novo genome assemblies for three species of parasitic nematodes (Brugia malayi, Trichuris trichiura, and Ancylostoma caninum) generated using only Oxford Nanopore Technologies MinION data. Assemblies were compared to current reference genomes and against additional assemblies that were supplemented with short-read Illumina data through polishing or hybrid assembly approaches. For each species, assemblies generated using only MinION data had similar or superior measures of contiguity, completeness, and gene content. In terms of gene composition, depending on the species, between 88.9 and 97.6% of complete coding sequences predicted in MinION data only assemblies …

Clinical Sensitivity And Time-To-Result Of A Cascaded Pooled Testing Approach For Assessing The Prevalence And Intensity Of Schistosoma Haematobium Infection, Abraham Degarege, Bruno Levecke, Yohannes Negash, Abebe Animut, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: This study compared the clinical sensitivity and the time-to-result of an individual testing (IT) and a cascaded pooled testing approach (CPT; a positive test result in a pooled sample triggers examination of smaller-sized pools or individual samples) for assessing the prevalence and the intensity of Schistosoma haematobium infection. We also compared the sensitivity of the CPT in detecting S. haematobium infection when deploying urine filtration microscopy (UFM) vs. urine reagent strips (URS), and testing 10 mL vs. 15 mL of urine.

METHODOLOGY/PRINCIPAL FINDINGS: Between October 2021 and April 2022, S. haematobium eggs were counted in urine samples collected from …

Dengueseq: A Pan-Serotype Whole Genome Amplicon Sequencing Protocol For Dengue Virus, Chantal B. F. Vogels, Verity Hill, Mallery I. Breban, Chrispin Chaguza, Lauren M. Paul, Afeez Sodeinde, Emma Taylor-Salmon, Isabel M. Ott, Mary E. Petrone, Dennis Dijk, Marcel Jonges, Matthijs R. A. Welkers, Timothy Locksmith, Yibo Dong, Namratha Tarigopula, Omer Tekin, Sarah Schmedes, Sylvia Bunch, Natalia Cano, Rayah Jaber, Charles Panzera, Ian Stryker, Julieta Vergara, Rebecca Zimler, Edgar Kopp, Lea Heberlein, Kaylee Herzog, Joseph R. Fauver, Andrea M. Morrison, Scott F. Michael, Nathan D. Grubaugh

Journal Articles: Epidemiology

BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes.

RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both …

Search Strategies For "Community Engagement Definition And Evaluation For Cancer Center: Scoping Review", Heidi Keeler, Brooke Fitzpatrick, Nicole Carritt, Emma Hymel, Josiane Kabayundo, Jordan Mccullough, Krishtee Napit, Regina Idoate, Shinobu Watanabe-Galloway

Search Strategies

No abstract provided.

Feasibility Assessment Of A Novel Isolation Care Tent In Uganda During The 2022, M. Jana Broadhurst, Rodgers R. Ayebare, David Brett-Major, Sean M. Carroll, Jacob Lacore, Alexander D. Laskey, James V. Lawler, Patricia Lord, Ruben M. Vazquez, Peter Waitt, Mohammed Lamorde

Journal Articles: Epidemiology

This case study describes a feasibility assessment of a novel isolation care tent used in health facilities in Uganda during the 2022 Sudan ebolavirus outbreak. The Isolation System for Treatment and Agile Response to High-Risk Infections Model 1B (ISTARI 1B) is a single-occupancy, portable, negative-pressure isolation tent designed for the safe delivery of standard care to patients with a communicable disease, including Ebola disease (Sudan). At the request of the Uganda Ministry of Health, the Makerere University Infectious Diseases Institute and University of Nebraska Medical Center partnered to evaluate 7 health facilities across 4 districts in Uganda for infrastructure, case …

Antimicrobial Activity Of Gallium(Iii) Compounds: Pathogen-Dependent Targeting Of Multiple Iron/Heme-Dependent Biological Processes, Seoung-Ryoung Choi, Mohammed A. Hassan, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth …

Editorial: Intersection Of Diet, Intestinal Microbiota, And Their Metabolites On Cancer Prevention, Nancy D. Turner, Tiffany L. Weir, Jacques Izard

Journal Articles: Internal Medicine

No abstract provided.

Natural Killer Cell Effector Function Is Critical For Host Defense Against Alcohol-Associated Bacterial Pneumonia, Daniel Villageliu, Kelly C. Cunningham, Deandra R. Smith, Daren L. Knoell, Mason Mandolfo, Todd A. Wyatt, Derrick R. Samuelson

Journal Articles: Internal Medicine

Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon …

Myc Overexpression In Natural Killer Cell Lymphoma: Prognostic And Therapeutic Implications, Chengfeng Bi, Yuhua Huang, Roshia Ali, Fang Wang, Xia Yang, Alyssa Bouska, Lu Xu, Xinbao Hao, Matthew A. Lunning, Wing C. Chan, Javeed Iqbal, Dennis D. Weisenburger, Julie M. Vose, Kai Fu

Journal Articles: Oncology and Hematology

The current clinical management of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the prognostic index of NK cells lymphoma with Epstein-Barr virus (PINK-E) prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown in NK …

Does Implementation Of A Lifestyle Medicine Curriculum Affect Student Wellness During Doctor Of Physical Therapy Education?, Betsy J. Becker, Kathleen G. Volkman, Tessa Wells, Nicole M. Sleddens, Teresa Cochran

Posters and Presentations: Physical Therapy

Background

Current healthcare environments amplify the need for educational systems to forge healthy workforces to withstand stressors. Our study examines the effects of embedding a lifestyle medicine curriculum on student wellness in a Doctor of Physical Therapy (DPT) Program, simultaneously preparing students to implement lifestyle medicine with future patients and communities.

Methods

In a DPT program, we implemented a lifestyle medicine curriculum grounded within the Social-Ecological Model. This framework emphasizes student success in the program’s pre-clinical phases, creates a purposeful “ripple effect” threading wellness strategies among peers, patients, and communities, and emphasizes wellness as a clinician over the 32-month curriculum. …

A Randomized Clinical Trial Of A Mobile Application That Supports Family Caregiver Participation In Icu Care, Breanna D. Hetland, Christina Bach, Jessica Castner, Erin Grotts, Mary Beth Happ, Jennifer M. Heusinkvelt, Kevin A. Kupzyk, Bunny J. Pozehl, Ellie Rubenfeld, Abigail Wawers

Posters and Presentations: College of Nursing

No abstract provided.

Evaluation Of Vitamin E Isoforms In Placental Tissue And Their Relationship With Maternal Dietary Intake And Plasma Concentrations In Mother-Infant Dyads, Ishani Jhamb, Alyssa Freeman, Michelle R. Lotfi, Matthew Van Ormer, Corrine K. Hanson, Ann Anderson-Berry, Melissa K. Thoene

Journal Articles: Pediatrics

α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal-fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy outcomes. However, little is known about tocopherol concentrations in placental tissue and their role in modulating placental oxidative stress, a process that is implicated in many complications of pregnancy. The objectives of this research are to evaluate the concentrations of α- and γ-tocopherol in placental tissue and assess relationships with maternal and umbilical cord plasma concentrations. A …

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M. Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette M. Smith, Ji Yuan, Hina Naushad Qureishi, Brian K. Link, Melissa H. Cessna, Paul M. Barr, Brad S. Kahl, Matthew S. Mckinney, Nadia Khan, Ranjana H. Advani, Peter Martin, Andre H. Goy, Tycel J. Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R. Flowers, Caron A. Jacobson, Sonali M. Smith, Deborah M. Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy Greiner, James O. Armitage, Matthew A. Lunning, Dennis D. Weisenburger, Gregory Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Journal Articles: Oncology and Hematology

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

Are We Really Listening? A Program To Assess And Mitigate Systemic Factors Contributing To Clinician Burnout, Sarah E. Richards, Victoria Kennel, Jana L. Wardian Phd, Kristy Carlson, Bethany Lowndes

Journal Articles: Hospital Medicine

Background: Many US physicians are experiencing burnout affecting patient care quality, safety, and experience. Institutions often focus on personal resilience instead of system-level issues. Our leaders developed a novel process to identify and prioritize key system-related stressors and work to mitigate factors that negatively impact clinician wellbeing through a structured Listening Campaign.

Methods: The Listening Campaign consists of meeting with each clinician group leader, a group Listening Session, a follow up meeting with the leader, a final report, and a follow-up session. During the Listening Session, clinicians engage in open discussion about what is going well, complete individual reflection worksheets …

Molecular Signaling Network And Therapeutic Developments In Breast Cancer Brain Metastasis, Mercilena Benjamin, Pushkar Malakar, Rohit Anthony Sinha, Mohd Wasim Nasser, Surinder K. Batra, Jawed A. Siddiqui, Bandana Chakravarti

Journal Articles: Biochemistry & Molecular Biology

Breast cancer (BC) is one of the most frequently diagnosed cancers in women worldwide. It has surpassed lung cancer as the leading cause of cancer-related death. Breast cancer brain metastasis (BCBM) is becoming a major clinical concern that is commonly associated with ER-ve and HER2+ve subtypes of BC patients. Metastatic lesions in the brain originate when the cancer cells detach from a primary breast tumor and establish metastatic lesions and infiltrate near and distant organs via systemic blood circulation by traversing the BBB. The colonization of BC cells in the brain involves a complex interplay in the tumor microenvironment (TME), …

Roles Unveiled For Membrane-Associated Mucins At The Ocular Surface Using A Muc4 Knockout Mouse Model, Rafael Martinez-Carrasco, Satyanarayan Rachagani, Surinder K. Batra, Pablo Argüeso, M Elizabeth Fini

Journal Articles: Biochemistry & Molecular Biology

Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc4 revealed a spiraling ribbon pattern across the corneal epithelium, consistent with centripetal cell migration from the limbus. Depletion of Muc4 compromised transcellular barrier function, as evidenced by an increase in rose bengal staining. In addition, the corneal surface was less smooth, consistent with disruption of tear film stability. While surface cells presented with well-developed microprojections, an increase in …

Microrna-1 Attenuates The Growth And Metastasis Of Small Cell Lung Cancer Through Cxcr4/Foxm1/Rrm2 Axis, Parvez Khan, Jawed A. Siddiqui, Prakash Kshirsagar Dr., Ramakanth Chirravuri Venkata, Shailendra K. Maurya, Tamara Mirzapoiazova, Naveenkumar Perumal, Sanjib Chaudhary, Ranjana K. Kanchan, Mahek Fatima, Md Arafat Khan, Asad Ur Rehman, Imayavaramban Lakshmanan, Sidharth Mahapatra, Geoffrey A. Talmon, Prakash Kulkarni, Apar Kishor Ganti, Maneesh Jain, Ravi Salgia, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.

METHODS: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, …

Gpcrs And Fibroblast Heterogeneity In Fibroblast-Associated Diseases, Nidhi V. Dwivedi, Souvik Datta, Karim El-Kersh, Ruxana Sadikot Md, Mrcp, Apar Kishor Ganti, Surinder K. Batra, Maneesh Jain

Journal Articles: Biochemistry & Molecular Biology

G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of "most targeted receptors". About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic …

Molecular And Metabolic Regulation Of Immunosuppression In Metastatic Pancreatic Ductal Adenocarcinoma, Shailendra K. Gautam, Surinder K. Batra, Maneesh Jain

Journal Articles: Biochemistry & Molecular Biology

Immunosuppression is a hallmark of pancreatic ductal adenocarcinoma (PDAC), contributing to early metastasis and poor patient survival. Compared to the localized tumors, current standard-of-care therapies have failed to improve the survival of patients with metastatic PDAC, that necessecitates exploration of novel therapeutic approaches. While immunotherapies such as immune checkpoint blockade (ICB) and therapeutic vaccines have emerged as promising treatment modalities in certain cancers, limited responses have been achieved in PDAC. Therefore, specific mechanisms regulating the poor response to immunotherapy must be explored. The immunosuppressive microenvironment driven by oncogenic mutations, tumor secretome, non-coding RNAs, and tumor microbiome persists throughout PDAC progression, …

Specific Targeting And Labeling Of Colonic Polyps In Cpc-Apc Mice With Mucin 5ac Fluorescent Antibodies: A Model For Detection Of Early Colon Cancer, Michael A. Turner, Kristin E. Cox, Shanglei Liu, Nicholas Neel, Siamak Amirfakhri, Hiroto Nishino, Mojgan Hosseini, Joshua A. Alcantara, Amer Ali Abd El-Hafeez, Thinzar M. Lwin, Kavita Mallya, Joseph R. Pisegna, Satish K. Singh, Pradipta Ghosh, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 …

Immunotherapy: An Emerging Modality To Checkmate Brain Metastasis, Aatiya Ahmad, Parvez Khan, Asad Ur Rehman, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

The diagnosis of brain metastasis (BrM) has historically been a dooming diagnosis that is nothing less than a death sentence, with few treatment options for palliation or prolonging life. Among the few treatment options available, brain radiotherapy (RT) and surgical resection have been the backbone of therapy. Within the past couple of years, immunotherapy (IT), alone and in combination with traditional treatments, has emerged as a reckoning force to combat the spread of BrM and shrink tumor burden. This review compiles recent reports describing the potential role of IT in the treatment of BrM in various cancers. It also examines …

Chimeric Antibody Targeting Unique Epitope On Onco-Mucin16 Reduces Tumor Burden In Pancreatic And Lung Malignancies, Ashu Shah, Sanjib Chaudhary, Imayavaramban Lakshmanan, Abhijit Aithal, Sophia G. Kisling, Claire Sorrell, Saravanakumar Marimuthu, Shailendra K. Gautam, Sanchita Rauth, Prakash Kshirsagar, Jesse L. Cox, Gopalakrishnan Natarajan, Rakesh Bhatia, Kavita Mallya, Satyanarayana Rachagani, Mohd W. Nasser, Apar Kishor Ganti, Ravi Salgia, Sushil Kumar, Maneesh Jain, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers. …

The Mucin Family Of Proteins: Candidates As Potential Biomarkers For Colon Cancer, Kristin E. Cox, Shanglei Liu, Thinzar M. Lwin, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

Mucins (MUC1-MUC24) are a family of glycoproteins involved in cell signaling and barrier protection. They have been implicated in the progression of numerous malignancies including gastric, pancreatic, ovarian, breast, and lung cancer. Mucins have also been extensively studied with respect to colorectal cancer. They have been found to have diverse expression profiles amongst the normal colon, benign hyperplastic polyps, pre-malignant polyps, and colon cancers. Those expressed in the normal colon include MUC2, MUC3, MUC4, MUC11, MUC12, MUC13, MUC15 (at low levels), and MUC21. Whereas MUC5, MUC6, MUC16, and MUC20 are absent from the normal colon and are expressed in colorectal …

Elevated Paf1-Rad52 Axis Confers Chemoresistance To Human Cancers, Sanchita Rauth, Koelina Ganguly, Pranita Atri, Seema Parte, Rama Krishna Nimmakayala, Venkatesh Varadharaj, Palanisamy Nallasamy, Raghupathy Vengoji, Ayoola O. Ogunleye, Imayavaramban Lakshmanan, Ramakanth Chirravuri, Mika Bessho, Jesse L. Cox, Jason M. Foster, Geoffrey A. Talmon, Tadayoshi Bessho, Apar Kishor Ganti, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression …

Restoration Of Normal Blood Flow In Atherosclerotic Arteries Promotes Plaque Stabilization, Morgan A. Schake, Ian S. Mccue, Evan T. Curtis, Thomas J. Ripperda, Samuel Harvey, Bryan T. Hackfort, Anna Fitzwater, Yiannis S. Chatzizisis, Forrest M. Kievit, Ryan M. Pedrigi

Journal Articles: Cellular & Integrative Physiology

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE^−/−) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuff was removed to allow restoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of …