Digital Commons Network^™

Management Of Anhedonia After Epilepsy Surgery, Gerardo Maria De Araujo Filho, Antonio L Teixeira

Faculty, Staff and Student Publications

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling …

Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic …

Higher Il-6 And Il-4 Plasma Levels In Depressed Elderly Women Are Influenced By Diabetes Mellitus, Natália S Dias, Antônio L Teixeira, Breno S Diniz, Erica L Vieira, Bernardo De M Viana, Izabela G Barbosa

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed at investigating a set of peripheral cytokines in elderly female patients with MDD, comparing them to controls, and assessing the potential influence of clinical comorbidities on inflammatory markers.

METHODS: Twenty-five elderly female patients diagnosed with MDD and 19 age-matched female controls were enrolled on this study. Plasma levels of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were evaluated with commercially-available assays.

RESULTS: Elderly female patients with MDD exhibited higher plasma IL-6 and IL-4 levels when compared to controls. In a logistic regression model taking cytokine levels, comorbidities, and age into account, only …

Fitness Consequences Of Depressive Symptoms Vary Between Generations: Evidence From A Large Cohort Of Women Across The 20th Century, Christopher I Gurguis, Renée A Duckworth, Nicole M Bucaro, Consuelo Walss-Bass

Faculty, Staff and Student Publications

Depression has strong negative impacts on how individuals function, leading to the assumption that there is strong negative selection on this trait that should deplete genetic variation and decrease its prevalence in human populations. Yet, depressive symptoms remain common. While there has been a large body of work trying to resolve this paradox by mapping genetic variation of this complex trait, there have been few direct empirical tests of the core assumption that there is consistent negative selection on depression in human populations. Here, we use a unique long-term dataset from the National Health and Nutrition Examination Survey that spans …

Induction Of Long-Term Hyperexcitability By Memory-Related Camp Signaling In Isolated Nociceptor Cell Bodies, Alexis Bavencoffe, Michael Y Zhu, Sanjay V Neerukonda, Kayla N Johnson, Carmen W Dessauer, Edgar T Walters

Faculty, Staff and Student Publications

Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation. This cAMP-PKA-CREB-gene transcription-protein synthesis pathway was tested using whole-cell current clamp methods on small dissociated sensory neurons (primarily nociceptors) from dorsal root ganglia (DRGs) excised from …

A Look-Up-Table Development To Facilitate Ct Simulation Of Mr-Linac Treatment, Neil Hughes, Travis C Salzillo, Sastry Vedam, Tze Yee Lim, Xin Wang, He Wang, Mustefa Mohammedsaid, Clifton D Fuller, Jihong Wang, Jinzhong Yang

Faculty, Staff and Student Publications

While current MR-Linac (MRL) treatment workflows utilize a large table overlay during CT simulation to convert indexing between the two machines, we developed a look-up-table (LUT) as an alternative approach. After populating the LUT, index conversion factors were verified at three separate table locations. The resultant root-mean-square isocenter shifts on the MRL were 0.04/0.08 cm, 0.08/0.07 cm, and 0.09/0.08 cm with/without using the table overlay during simulation in the lateral, longitudinal, and vertical directions, respectively, which is within registration tolerance. Clinical implementation of the LUT has resulted in a more efficient MRL treatment workflow while maintaining accurate patient setup.

Clic1-Mediated Autophagy Confers Resistance To Ddp In Gastric Cancer, Zhen-Liang Nong, Kun Zhao, Ye Wang, Zhu Yu, Cong-Jun Wang, Jun-Qiang Chen

Faculty, Staff and Student Publications

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular …

First Evidence Of Microplastic Inhalation Among Free-Ranging Small Cetaceans, Miranda K Dziobak, Andreas Fahlman, Randall S Wells, Ryan Takeshita, Cynthia Smith, Austin Gray, John Weinstein, Leslie B Hart

Faculty, Staff and Student Publications

Plastic is a ubiquitous environmental contaminant, resulting in widespread exposure across terrestrial and marine spaces. In the environment, plastics can degrade into microparticles where exposure has been documented in a variety of fauna at all trophic levels. Human epidemiological studies have found relationships between inhaled microplastics and oxidative stress and inflammation. Previous studies of bottlenose dolphins (Tursiops truncatus) have reported prevalent exposure to plasticizing chemicals (e.g., phthalates) as well as particle loads in gastrointestinal tracts, but exposure from inhalation has not yet been studied. The objective of this study was to determine if inhalation is a viable route of microplastic …

Protein-Centric Omics Analysis Reveals Circulating Complements Linked To Non-Viral Liver Diseases As Potential Therapeutic Targets, Yingzhou Shi, Hang Dong, Shiwei Sun, Xiaoqin Wu, Jiansong Fang, Jianbo Zhao, Junming Han, Zongyue Li, Huixiao Wu, Luna Liu, Wanhong Wu, Yang Tian, Guandou Yuan, Xiude Fan, Chao Xu

Faculty, Staff and Student Publications

BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.

METHODS: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.

RESULTS: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk …

Association Of Perceived Neighborhood Air Quality Problems With Attempt To Quit Cigarette Smoking: A Cross-Sectional Study In Texas, Monalisa Chandra, Joel Fokom Domgue, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Background: Cigarette smoking is the major preventable cause of premature deaths in the United States. Attempting to quit smoking is an important step toward smoking cessation. Although it has been studied extensively, limited information on the association between attempts to quit smoking and neighborhood air quality problems is available. Therefore, we examined the association between attempts to quit smoking in the past year and perceived neighborhood air quality problems among adult Texans who smoke.

Methods: In 2018, a cross-sectional multistage area probability design-based survey was administered to collect sociodemographic, behavioral, and health-related information from a representative sample of 2050 Texas …

Prevalence And Disparities In Receiving Medical Advice To Quit Tobacco Use In The Us Adult Population, Monalisa Chandra, Rajesh Talluri, Joel Fokom Domgue, Sanjay Shete

Faculty, Staff and Student Publications

Introduction: Evidence suggests that advice from health care professionals (HCP) increases the likelihood of quit attempts and successful quitting of tobacco use. However, previous studies primarily focussed on cigarette smoking and did not include all forms of tobacco products. This study aimed to investigate the prevalence and disparities in receiving HCP's advice to quit tobacco use (combustible or noncombustible) in the US adult population.

Methods: Using the 2022 National Health Information Survey (NHIS) data, we examined 4,424 adults who reported (i) any tobacco product use within the past 12 months and (ii) having seen an HCP within the past 12 …

Endovascular Interventions In Cancer Patients With Compromise Of The Mediastinal Vasculature: A Review, Steven Yevich, Nicolas Cardenas, Rahul Sheth, Joshua Kuban, Milan Patel, Ketan Shah, Koustav Pal, Stephen R Chen, Alda Tam

Faculty, Staff and Student Publications

The mediastinal vasculature can be affected by various etiologies in cancer patients. Both direct and indirect sequela of cancer may result in life-threatening clinical presentations. Tumor growth may cause vessel narrowing and decreased blood flow from either extrinsic mass effect, invasion into the vascular wall, or tumor thrombus within the lumen. In addition, cancer patients are predisposed to indirect sequela to the mediastinal vasculature from an increased risk of benign thromboembolic events, tumor thrombus, or iatrogenic complications during cancer treatments. Benign thrombus may result in partial or complete occlusion of the superior vena cava (SVC) or pulmonary artery. Vascular damage …

A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer

Faculty, Staff and Student Publications

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing …

Research Hot Spots And Trends In Endocrine-Related Adverse Events Caused By Immune Checkpoint Inhibitors: A Bibliometric Analysis And Visualization Research, Jun Zhao, Guangwei Liu, Xue Yang, Chuanzhou Zhang, Bing Han, Man Jiang

Faculty, Staff and Student Publications

Background: In recent years, with the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment, the toxicity associated with immunotherapy of ICIs has attracted more attention from scholars. Endocrine toxicity is the most likely immune-related adverse events (irAEs) and is often irreversible, posing a significant clinical treatment challenge.

Methods: In this study, bibliometric methods were used to analyze relevant literature in screening endocrine-related adverse events caused by ICIs in the Web of Science core collection database (WoSCC) and to summarize the status, research hot spots, and future trends in this field.

Results: 321 countries, 297 institutions, 365 authors, and …

Camrelizumab Combined With Apatinib And Nanoparticle Albumin-Bound Paclitaxel In Lung Adenocarcinoma (Capap-Lung): A Single-Arm Phase Ii Study, Xingxiang Pu, Gen Lin, Maoliang Xiao, Jie Lin, Qianzhi Wang, Yi Kong, Xuejun Yan, Fang Xu, Yan Xu, Jia Li, Kang Li, Bolin Chen, Xiaoping Wen, Yali Tan, Fengzhuo Cheng, Kangle Zhu, Na Li, Lin Wu

Faculty, Staff and Student Publications

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma.

Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma …

Knowledge Mapping Of Anaplastic Thyroid Cancer Treatments: A Bibliometric Analysis (2000–2023), Shiqiang Liu, Xingmin Yan, Yalong Yang, Yun Xia, Panshi Zhang

Faculty, Staff and Student Publications

Context: Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature.

Methodology: A systematic search was …

Combining Egfr And Kras G12c Inhibitors For Kras G12c Mutated Advanced Colorectal Cancer, Hirotaka Miyashita, David S Hong

Faculty, Staff and Student Publications

KRAS is a commonly mutated gene in advanced colorectal cancer (CRC). Recently, inhibitors of KRAS G12C were developed and have shown promising efficacy for KRAS G12C mutated non-small cell lung cancer. However, KRAS G12C inhibitor monotherapy has not demonstrated excellent efficacy for KRAS G12C mutated advanced CRC due to multiple resistance mechanisms, especially receptor tyrosine kinase (RTK) signaling activation. To overcome this resistance mechanism, various combinations of epithelial growth factor receptor (EGFR) and KRAS G12C inhibitors, including panitumumab plus sotorasib, have been investigated in clinical trials. The combination of EGFR and KRAS G12C inhibitors for KRAS G12C mutated CRC demonstrated …

Sotorasib With Panitumumab In Chemotherapy-Refractory Kras G12c-Mutated Colorectal Cancer: A Phase 1b Trial, Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger, Toshiki Masuishi, Edward J Kim, Christine M Bestvina, Scott Kopetz, Gerald S Falchook, Corey Langer, John Krauss, Sonam Puri, Panli Cardona, Emily Chan, Tracy Varrieur, Lata Mukundan, Abraham Anderson, Qui Tran, David S Hong

Faculty, Staff and Student Publications

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRAS

Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby

Faculty, Staff and Student Publications

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17).

METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, …

Exploring Measurement Tools Used To Assess Knowledge, Attitudes, And Perceptions Of Pregnant Women Toward Prenatal Screening: A Systematic Review, Lea Sacca, Yasmine Zerrouki, Sara Burgoa, Goodness Okwaraji, Ashlee Li, Shaima Arshad, Maria Gerges, Stacey Tevelev, Sophie Kelly, Michelle Knecht, Panagiota Kitsantas, Robert Hunter, Laurie Scott, Alexis Piccoli Reynolds, Gabriela Colon, Michele Retrouvey

Faculty, Staff and Student Publications

There is a lack of standardized measurement tools globally to assess knowledge, attitudes, and perceptions of expecting women toward prenatal screening. The purpose of this systematic review was to identify reasons women pursue or decline prenatal screening and compare the strengths and limitations of available measurement tools used to assess pregnant women's perceptions, knowledge, and attitudes toward prenatal screening. This review followed the five-step York methodology by Arksey and O'Malley and incorporated recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist for the extraction, analysis, and presentation of results. The five steps consisted of: (1) identification of …

From Transcriptomics To Digital Twins Of Organ Function, Jens Hansen, Abhinav R Jain, Philip Nenov, Peter N Robinson, Ravi Iyengar

Faculty, Staff and Student Publications

Cell level functions underlie tissue and organ physiology. Gene expression patterns offer extensive views of the pathways and processes within and between cells. Single cell transcriptomics provides detailed information on gene expression within cells, cell types, subtypes and their relative proportions in organs. Functional pathways can be scalably connected to physiological functions at the cell and organ levels. Integrating experimentally obtained gene expression patterns with prior knowledge of pathway interactions enables identification of networks underlying whole cell functions such as growth, contractility, and secretion. These pathways can be computationally modeled using differential equations to simulate cell and organ physiological dynamics …

Egfr, Hla-G, Cd70, C-Met, And Ny-Eso1 As Potential Biomarkers In High Grade Epithelial Ovarian Carcinoma, Duc Vo, Yan Liu, Anil K Sood, Katy Rezvani, Amir A Jazaeri, Jinsong Liu

Faculty, Staff and Student Publications

High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of …

Expert-Centered Evaluation Of Deep Learning Algorithms For Brain Tumor Segmentation, Katharina V Hoebel, Christopher P Bridge, Sara Ahmed, Oluwatosin Akintola, Caroline Chung, Raymond Y Huang, Jason M Johnson, Albert Kim, K Ina Ly, Ken Chang, Jay Patel, Marco Pinho, Tracy T Batchelor, Bruce R Rosen, Elizabeth R Gerstner, Jayashree Kalpathy-Cramer

Faculty, Staff and Student Publications

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of …

Nontuberculosis Mycobacteria (Ntm) Infections In Patients With Leukemia: A Single Center Case Series, Jennifer Marvin-Peek, Koji Sasaki, Dimitrios P Kontoyiannis, Javier Adachi, Maro Ohanian, Koichi Takahashi, Ghayas C Issa, Steven Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with …

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …

Canadian French Translation And Validation Of The Neck Dissection Impairment Index: A Quality Of Life Measure For The Surgical Oncology Population, Michel Khoury, William Guertin, Cameo Hao, Mikhail Saltychev, Tareck Ayad, Eric Bissada, Apostolos Christopoulos, Sami Moubayed, Marie-Jo Olivier, Douglas Chepeha, Stephen Y Lai, Anastasios Maniakas

Faculty, Staff and Student Publications

BACKGROUND: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French.

METHODS: A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session …

Differing Impacts Of The Covid-19 Pandemic On Farmers And Intermediaries: Insights Into The Ecuadorian Cocoa Value Chain, Guillermo Zambrano, Lina M Tennhardt, Moritz Egger, Karen Ramírez, Adriana Santos, Byron Moyano, Michael Curran

Faculty, Staff and Student Publications

The COVID-19 pandemic generated diverse impacts and responses in agricultural value chains worldwide. Cocoa is a key crop for Ecuadorian exports, and the analysis of effects the pandemic had on value chain actors contributes to the understanding of their individual capacities to coping with a major shock. The purpose of this study was to assess the number and severity of impacts and responses implemented by two links in the cocoa value chain to the pandemic, based on a survey of 158 cocoa farmers and 52 cocoa intermediaries from the main cocoa-producing provinces of the northern coast of Ecuador in 2021. …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Early And Rapid Development Of Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation, Jacqueline S Dickey, Burton F Dickey, Amin M Alousi, Richard E Champlin, Ajay Sheshadri

Faculty, Staff and Student Publications

Bronchiolitis obliterans (BO) is a form of graft-versus-host disease (GVHD) in the lung and manifests as moderate to severe airflow obstruction after hematopoietic stem cell transplantation (HCT). New-onset airflow obstruction on spirometry is considered diagnostic of bronchiolitis obliterans syndrome (BOS). BOS affects about 5% of all HCT recipients. In general, BO is thought of as a late complication of HCT, usually occurring after day 100 post-transplantation. However, the onset of airflow obstruction can be rapid and is most often irreversible even with treatment. We describe a patient who rapidly developed severe airflow obstruction less than one month after transplantation following …

Epigallocatechin Gallate Regulates The Myeloid-Specific Transcription Factor Pu1 In Macrophages, Manjula Karpurapu, Kavita Kumari Kakarala, Sangwoon Chung, Yunjuan Nie, Amritendu Koley, Patrick Dougherty, John W Christman

Faculty, Staff and Student Publications

Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.1 in macrophages ameliorated LPS-induced acute lung injury (ALI) in bone marrow chimera mice. Inhibitors that block the transcriptional activity of PU.1 in macrophages have the potential to mitigate the pathophysiology of LPS-induced ALI. However, complete inactivation of PU.1 gene disrupts normal myelopoiesis. Although the green tea polyphenol Epigallocatechin gallate (EGCG) has been shown to regulate inflammatory genes in various cell types, it is not known if EGCG alters the transcriptional activity of PU.1 protein. Using Schrodinger Glide docking, we have …