Medicine and Health Sciences Commons^™

Biomarkers Of Toxic Exposure And Oxidative Stress Among U.S. Adult Users Of Premium Cigar Versus Other Cigar Subtypes: 2013-2019, Hongying Dai, Neal L. Benowitz, Eleanor Rogan, Abraham Degarege, James Buckley, Ali S. Khan

Journal Articles: Epidemiology

INTRODUCTION: Cigars are currently the second-highest-used combustible tobacco product among U.S. adults, but knowledge about health effects of premium cigars versus other cigar subtype use is limited.

AIMS AND METHODS: This study analyzed the biospecimen data (n = 31 875) from Waves 1-5 of the Population Assessment of Tobacco and Health Study, collected during 2013-2019. Multivariable generalized estimation equations, accounting for within-person clustering, were conducted to examine differences in urine biomarkers of exposure (BOE) from five classes of harmful and potentially harmful constituents along with a biomarker of oxidative stress (urine 8-isoprostane) among exclusive users of premium cigars versus other …

Liquid Biopsies To Occult Brain Metastasis, Asad Ur Rehman, Parvez Khan, Shailendra K. Maurya, Jawed A. Siddiqui, Juan A. Santamaria-Barria, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the …

Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

OBJECTIVE: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

METHODS: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples. Image registration and machine learning algorithms were developed to largely automate an imaging analysis pipeline identifying distinct cell …

Acute Encephalopathy With Elevated Csf Inflammatory Markers As The Initial Presentation Of Covid-19, Shelli Farhadian, Laura R. Glick, Chantal B. F. Vogels, Jared Thomas, Jennifer Chiarella, Arnau Casanovas-Massana, Jing Zhou, Camila Odio, Pavithra Vijayakumar, Bertie Geng, John Fournier, Santos Bermejo, Joseph R. Fauver, Tara Alpert, Anne L. Wyllie, Cynthia Turcotte, Matthew Steinle, Patrick Paczkowski, Charles Dela Cruz, Craig Wilen, Albert I. Ko, Sean Mackay, Nathan D. Grubaugh, Serena Spudich, Lydia Aoun Barakat

Journal Articles: Epidemiology

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients.

CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion.

CONCLUSION: Our findings …

Primary Sclerosing Epithelioid Fibrosarcoma Of Kidney With Variant Histomorphologic Features: Report Of 2 Cases And Review Of The Literature., Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Oguz Aydin, Julia A. Bridge, Berrin Buyukeren, Fazil Tuncay Aki

Journal Articles: Pathology and Microbiology

The authors present two cases of primary sclerosing epithelioid fibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Day-To-Day Fluctuation Of Point-Of-Care Circulating Cathodic Antigen Test Scores And Faecal Egg Counts In Children Infected With Schistosoma Mansoni In Ethiopia, Abraham Degarege, Mengistu Legesse, Girmay Medhin, Tilahun Teklehaymanot, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Determining the variation of circulating cathodic antigen (CCA) in urine and egg counts variation in stool between days in Schistosoma mansoni (S. mansoni) infected individuals is vital to decide whether or not to rely on a single-sample test for diagnosis of Schistosomiasis. In this study, the magnitude of day-to-day variation in urine-CCA test scores and in faecal egg counts was evaluated in school children in Ethiopia.

METHODS: A total of 620 school children (age 8 to 12 years) were examined for S. mansoni infection using double Kato-Katz and single urine-CCA cassette methods (batch 32727) on three consecutive days.

RESULTS: …

Cytoplasmic Localization Of Alteration/Deficiency In Activation 3 (Ada3) Predicts Poor Clinical Outcome In Breast Cancer Patients., Sameer Mirza, Emad A. Rakha, Alaa Alshareeda, Shakur Mohibi, Xiangshan Zhao, Bryan J. Katafiasz, Jun Wang, Channabasavaiah B. Gurumurthy, Aditya Bele, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Transcriptional activation by estrogen receptor (ER) is a key step to breast oncogenesis. Given previous findings that ADA3 is a critical component of HAT complexes that regulate ER function and evidence that overexpression of other ER coactivators such as SRC-3 is associated with clinical outcomes in breast cancer, the current study was designed to assess the potential significance of ADA3 expression/localization in human breast cancer patients. In this study, we analyzed ADA3 expression in breast cancer tissue specimens and assessed the correlation of ADA3 staining with cancer progression and patient outcome. Tissue microarrays prepared from large series of breast cancer …

Overexpression Of A Novel Cell Cycle Regulator Ecdysoneless In Breast Cancer: A Marker Of Poor Prognosis In Her2/Neu-Overexpressing Breast Cancer Patients., Xiangshan Zhao, Sameer Mirza, Alaa Alshareeda, Ying Zhang, Channabasavaiah B. Gurumurthy, Aditya Bele, Jun Hyun Kim, Shakur Mohibi, Monica Goswami, Subodh M. Lele, William West, Fang Qiu, Ian O. Ellis, Emad A. Rakha, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression …

Renal Thrombotic Microangiopathy In Mice With Combined Deletion Of Endocytic Recycling Regulators Ehd3 And Ehd4., Manju George, Mark A. Rainey, Mayumi Naramura, Kirk W. Foster, Melissa S. Holzapfel, Laura L. Willoughby, Guoguang Ying, Rasna M. Goswami, Channabasavaiah B. Gurumurthy, Vimla Band, Simon C. Satchell, Hamid Band

Journal Articles: Eppley Institute

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3(-/-) mice and assessed renal development and pathology. Ehd3(-/-) animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3(-/-) mice and suggested functional compensation, we generated and analyzed Ehd3(-/-); Ehd4(-/-) mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between …

Sox11 Expression Is Highly Specific For Mantle Cell Lymphoma And Identifies The Cyclin D1-Negative Subtype., Ana Mozos, Cristina Royo, Elena Hartmann, Daphne De Jong, Cristina Baró, Alexandra Valera, Kai Fu, Dennis D. Weisenburger, Jan Delabie, Shih-Sung Chuang, Elaine S. Jaffe, Carmen Ruiz-Marcellan, Sandeep Dave, Lisa Rimsza, Rita Braziel, Randy D. Gascoyne, Francisco Solé, Armando López-Guillermo, Dolors Colomer, Louis M. Staudt, Andreas Rosenwald, German Ott, Pedro Jares, Elias Campo

Journal Articles: Pathology and Microbiology

BACKGROUND: Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.

DESIGN AND METHODS: The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin …

Clinical Implication Of Genome-Wide Profiling In Diffuse Large B-Cell Lymphoma And Other Subtypes Of B-Cell Lymphoma., Javeed Iqbal, Shantaram Joshi, Kavita N. Patel, Sofi I. Javed, Can Kucuk, Afeera Aabida, Francesco D'Amore, Kai Fu

Journal Articles: Pathology and Microbiology

The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely …