Digital Commons Network^™

Affinity-Tagged Smad1 And Smad5 Mouse Lines Reveal Transcriptional Reprogramming Mechanisms During Early Pregnancy, Zian Liao, Suni Tang, Kaori Nozawa, Keisuke Shimada, Masahito Ikawa, Diana Monsivais, Martin Matzuk

Faculty, Staff and Students Publications

Endometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci (Smad1^HA/HA and Smad5^PA/PA). By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated …

Fair Header Reference Genome: A Trustworthy Standard, Adam Wright, Mark D Wilkinson, Christopher Mungall, Scott Cain, Stephen Richards, Paul Sternberg, Ellen Provin, Jonathan L Jacobs, Scott Geib, Daniela Raciti, Karen Yook, Lincoln Stein, David C Molik

Faculty, Staff and Students Publications

The lack of interoperable data standards among reference genome data-sharing platforms inhibits cross-platform analysis while increasing the risk of data provenance loss. Here, we describe the FAIR bioHeaders Reference genome (FHR), a metadata standard guided by the principles of Findability, Accessibility, Interoperability and Reuse (FAIR) in addition to the principles of Transparency, Responsibility, User focus, Sustainability and Technology. The objective of FHR is to provide an extensive set of data serialisation methods and minimum data field requirements while still maintaining extensibility, flexibility and expressivity in an increasingly decentralised genomic data ecosystem. The effort needed to implement FHR is low; FHR's …

Reinforced Tissue Matrix To Strengthen The Abdominal Wall Following Reversal Of Temporary Ostomies Or To Treat Incisional Hernias, Spencer P Lake, Corey R Deeken, Amit K Agarwal

Faculty, Staff and Student Publications

BACKGROUND: Abdominal wall deficiencies or weakness are a common complication of temporary ostomies, and incisional hernias frequently develop after colostomy or ileostomy takedown. The use of synthetic meshes to reinforce the abdominal wall has reduced hernia occurrence. Biologic meshes have also been used to enhance healing, particularly in contaminated conditions. Reinforced tissue matrices (RTMs), which include a biologic scaffold of native extracellular matrix and a synthetic component for added strength/durability, are designed to take advantage of aspects of both synthetic and biologic materials. To date, RTMs have not been reported to reinforce the abdominal wall following stoma reversal.

AIM: To …

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Tajhal D Patel, Sandra L Grimm, Rupa S Kanchi, Tanmay Gandhi, Amrit Koirala, Jason T Yustein, Cristian Coarfa

Faculty, Staff and Students Publications

Osteosarcoma is the most prevalent bone tumor in pediatric patients. Neoadjuvant chemotherapy has improved osteosarcoma patient survival, however the 5-year survival rate for localized osteosarcoma is 75% with a 30-50% recurrence rate. We, therefore, sought to identify a prognostic gene signature which could predict poor prognosis in localized osteosarcoma patients. Using the TARGET osteosarcoma transcriptomic dataset, we identified a 13-hub gene signature associated with overall survival and time to death of localized osteosarcoma patients, with the high-risk group showing a 22% and the low-risk group showing 100% overall survival. Furthermore, network analysis identified five modules of co-expressed genes that significantly …

Sex-Based Differences In Melanoma Survival Improvement From 2004 To 2018, Vikram R Shaw, Angela Hudock, Baoyi Zhang, Christopher Amos, Chao Cheng

Faculty, Staff and Students Publications

Simple Summary

Melanoma is the deadliest form of skin cancer and its incidence and mortality may vary by demographic factors, such as sex, age, race, and socioeconomic status. Few studies, however, have characterized disparities in survival improvement across these demographic groups in melanoma. In the present study, the authors highlight disparities in melanoma survival improvement, both in diagnosed melanoma and carcinoma in situ. While melanoma survival has improved overall, some patient subgroups have experienced a lower improvement in survival from 2004 to 2018.

Abstract

Background: Melanoma is the deadliest form of skin cancer and its incidence and mortality vary by …

Study Protocol: Identifying Transcriptional Regulatory Alterations Of Chronic Effects Of Blast And Disturbed Sleep In United States Veterans, Molly J. Sullan, Kelly A. Stearns-Yoder, Zhaoyu Wang, Andrew J. Hoisington, Adam D. Brenoweth, Walter Carr, Yongchao Ge, Hanga Galfalvy, Fatemah Haghighi, Lisa A. Brenner

Faculty Publications

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of …

Raf Inhibitor Re-Challenge Therapy In Braf-Aberrant Pan-Cancers: The Re-Raffle Study, Blessie Elizabeth Nelson, Jason Roszik, Jibran Ahmed, Carmelia Maria Noia Barretto, Mirella Nardo, Erick Campbell, Amber M Johnson, Sarina A Piha-Paul, Isabella C Glitza Oliva, Shiao-Pei Weathers, Maria Cabanillas, Milind Javle, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable …

A Therapeutically Targetable Positive Feedback Loop Between Nc-Hlx-2-7, Hlx, And Myc That Promotes Group 3 Medulloblastoma, Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Brigette Romero, Mona Batish, Stacie Stapleton, George Jallo, Elayaraja Kolanthai, Sudipta Seal, Olivier Saulnier, Michael D Taylor, Robert J Wechsler-Reya, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse …

A Novel Machine Learning Algorithm Selects Proteome Signature To Specifically Identify Cancer Exosomes, Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri

Faculty, Staff and Student Publications

Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing …

Identifying Potential Dietary Treatments For Inherited Metabolic Disorders Using Drosophila Nutrigenomics, Felipe Martelli, Jiayi Lin, Sarah Mele, Wendy Imlach, Oguz Kanca, Christopher K Barlow, Jefferson Paril, Ralf B Schittenhelm, John Christodoulou, Hugo J Bellen, Matthew D W Piper, Travis K Johnson

Faculty, Staff and Students Publications

Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and rescues development, neurophysiology, …

New Onset Dyspnea In A Patient With Pacemaker, What Does The Ecg Tracing Show?, Jakob Nypaver, Robert Libera Do, Arun Kundra, Ravi Choxi

Transformative Medicine

Dual chamber pacemakers are programmed to allow for AV synchrony. Whenever a patient with a dual chamber pacemaker with underlying sinus rhythm presents with AV dissociation, the lack of AV synchrony should be questioned. The authors present a case of new onset dyspnea diagnosed as pacemaker syndrome. The diagnosis was initially delayed due to underlying ventricular paced rhythm as misidentified as normal pacemaker behavior.

A 69-year-old female with a past medical history of 2:1 atrioventricular block status post dual-chamber pacemaker implant presented with complaints of new onset shortness of breath and dyspnea. The ECG showed a ventricular rate of 66 …

Altered Lipid Metabolism In Apc-Driven Colorectal Cancer: The Potential For Therapeutic Intervention, Courtney O. Kelson, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Altered lipid metabolism is a well-recognized feature of solid cancers, including colorectal cancer. In colorectal cancer, upregulation of lipid metabolism contributes to initiation, progression, and metastasis; thus, aberrant lipid metabolism contributes to a poor patient outcome. The inactivating mutation of APC, a vital tumor suppressor in the Wnt signaling pathway, is a key event that occurs early in the majority of colorectal cancer cases. The potential crosstalk between lipid metabolism and APC-driven colorectal cancer is poorly understood. This review collectively highlights and summarizes the limited understanding between mutations in APC and the upregulation of Wnt/beta- catenin signaling and lipid metabolism. …

Extend The Benchmarking Indel Set By Manual Review Using The Individual Cell Line Sequencing Data From The Sequencing Quality Control 2 (Seqc2) Project, Binsheng Gong, Dan Li, Yifan Zhang, Rebecca Kusko, Samir Lababidi, Zehui Cao, Mingyang Chen, Ning Chen, Qiaochu Chen, Qingwang Chen, Jiacheng Dai, Qiang Gan, Yuechen Gao, Mingkun Guo, Gunjan Hariani, Yujie He, Wanwan Hou, He Jiang, Garima Kushwaha, Jian-Liang Li, Jianying Li, Yulan Li, Liang-Chun Liu, Ruimei Liu, Shiming Liu, Edwin Meriaux, Mengqing Mo, Mathew Moore, Tyler J Moss, Quanne Niu, Ananddeep Patel, Luyao Ren, Nedda F Saremi, Erfei Shang, Jun Shang, Ping Song, Siqi Sun, Brent J Urban, Danke Wang, Shangzi Wang, Zhining Wen, Xiangyi Xiong, Jingcheng Yang, Lihui Yin, Chao Zhang, Ruolan Zhang, Ambica Bhandari, Wanshi Cai, Agda Karina Eterovic, Dalila B Megherbi, Tieliu Shi, Chen Suo, Ying Yu, Yuanting Zheng, Natalia Novoradovskaya, Renee L Sears, Leming Shi, Wendell Jones, Weida Tong, Joshua Xu

Faculty, Staff and Student Publications

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly …

Tmem106b Coding Variant Is Protective And Deletion Detrimental In A Mouse Model Of Tauopathy, George A Edwards, Caleb A Wood, Yang He, Quynh Nguyen, Peter J Kim, Ruben Gomez-Gutierrez, Kyung-Won Park, Yong Xu, Cody Zurhellen, Ismael Al-Ramahi, Joanna L Jankowsky

Duncan NRI Faculty and Staff Publications

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and …

Unraveling Sorafenib Resistance In Hepatocellular Carcinoma: Exploring Key Facets, Dennis Kwabiah, Kyle Doxtater, Yamile Abuchard, Sophia Leslie, Ricardo Pequeno Bracho, Shaibir Hussain, Manish K. Tripathi

Research Symposium

Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated …

Advancing Primary Ciliary Dyskinesia Diagnosis Through High-Speed Video Microscopy Analysis, Wilfredo De Jesús-Rojas, Zachary J Demetriou, José Muñiz-Hernández, Gabriel Rosario-Ortiz, Frances M Quiñones, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency …

The Role Of Long Noncoding Rnas In Ocular Angiogenesis And Vascular Oculopathy, Pranali Gandhi, Yuzhi Wang, Guigang Li, Shusheng Wang

School of Medicine Faculty Publications

Background: Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides in length that do not code for proteins. Initially considered a genomic mystery, an increasing number of lncRNAs have been shown to have vital roles in physiological and pathological conditions by regulating gene expression through diverse mechanisms depending on their subcellular localization. Dysregulated angiogenesis is responsible for various vascular oculopathies, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and corneal neovascularization. While anti-VEGF treatment is available, it is not curative, and long-term outcomes are suboptimal, and some patients are unresponsive. Results and summary: To better understand these diseases, …

Ongoing Study Of The Association Of Apoe Gene Polymorphisms With Cognitive Impairment In The Rio Grande Valley Hispanic Population, Jaime Miguel L. Saveron, Daniela Gamez, Chun Xu

Research Symposium

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, exhibits a significant genetic component. In addition, mild cognitive impairment (MCI) is a key risk factor for AD. While certain demographic factors and genetic variants associated with AD and cognitive impairment have been identified in non-Hispanic populations, limited research exists on this subject within the Hispanic population, particularly in the Rio Grande Valley. This study aims to investigate the relationship between the APOE gene, specifically its ε4 allele, and cognitive impairment in the Hispanic population of the Rio Grande Valley.

Methods: A total of 269 Hispanic subjects, aged 60 and above, with …

Lncrna Impact On Regorafenib Resistance In Colorectal Cancer, Ricardo Pequeno Bracho, Kyle Doxtater, Dennis Kwabiah, Yamile Abuchard Anaya, Sophia Leslie, Mohammad Shabir Hussain, Manish Tripathi

Research Symposium

Cancer metastasis is one of the deadliest aspects of the disease, with about 90% of all cancer-related deaths due to its development at different sites within the body. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States, with 40-50% of all patients developing metastasis at some point during their fight with the disease. With the approval of Regorafenib for treating metastatic colorectal cancer, steps have been taken to combat metastasis in colorectal cancer. A vital aspect of the development of metastasis is the development of resistance to first-line chemotherapy. Regorafenib is an oral small-molecule …

Influence Of Neurotoxin Load On Parkinson’S Disease Pathophysiology, Abhishekh Pokhrel, Daniel Salinas, Nawaz Hack, Kelsey Potter-Baker

Research Symposium

Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder impacting movement, mood, and cognition. Among those affected, veterans, due to their occupational exposures, are particularly susceptible, contributing to over 110,000 PD cases in the United States. Studies have largely attributed this increased prevalence among veterans to environmental neurotoxins such as Agent Orange, MPTP, and 6-OHDA. However, it remains unclear how neurotoxin exposure load influences biological mechanisms in PD. This study aims to elucidate the influence of neurotoxin load on PD-associated molecular changes, neuroplasticity, neurodegeneration, and cognitive and motor function within a clinical population of the Rio Grande Valley region …

Highlights Of The 2023 Brano Heart Failure Forum, Bela Merkely, Rajko Radovancevic, Bojan Vrtovec, Igor D. Gregoric

The VAD Journal

Since 2007, the Branislav “Brano” Radovancevic Heart Failure Forum (BHFF) has been held annually to provide a venue for experts to present and discuss “Innovations and New Treatment Strategies in Heart Failure.” Clinicians and researchers gather yearly in a different Eastern European city to discuss the latest in heart failure diagnostics and therapeutics. The 2023 BHHF forum was held on the 13^th thru 15^th of September 2023 in Budapest, Hungary. It was attended by over 100 faculty from 16 countries. In addition, participation through online streaming was available. Throughout the forum, 16 sessions focused on challenges and solutions …

Student Perspectives On Transition From Bachelor’S To Master’S Degree For Professional Athletic Trainers: Advantages And Disadvantages, Bobbi A. Severt, Michael B. Phillips, Janet Kesterson Isbell

Internet Journal of Allied Health Sciences and Practice

Purpose: The purpose of this study is to understand the perspectives of students interested in a career in athletic training on the degree change and what they perceive as advantages and disadvantages to pursuing a master's level professional degree in athletic training. Method: A case study was conducted using an interpretivism framework informed by a constructionism theoretical stance. A focus group of six current undergraduate pre-athletic training students and individual interviews of three pre-athletic training graduates along with current and historical documents were used to collect data. An inductive approach was used to analyze data along with reflexive thematic analysis …

Childhood Cancer Mutagenesis Caused By Transposase-Derived Pgbd5, Makiko Yamada, Ross R Keller, Rodrigo Lopez Gutierrez, Daniel Cameron, Hiromichi Suzuki, Reeti Sanghrajka, Jake Vaynshteyn, Jeffrey Gerwin, Francesco Maura, William Hooper, Minita Shah, Nicolas Robine, Phillip Demarest, N Sumru Bayin, Luz Jubierre Zapater, Casie Reed, Steven Hébert, Ignas Masilionis, Ronan Chaligne, Nicholas D Socci, Michael D Taylor, Claudia L Kleinman, Alexandra L Joyner, G Praveen Raju, Alex Kentsis

Faculty, Staff and Students Publications

Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one of the most common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development in multiple developmentally accurate mouse models of Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop tumors, while maintaining normal cerebellar development. Ectopic activation of SHH signaling is sufficient to enforce cerebellar granule cell progenitor-like cell states, which exhibit Pgbd5-dependent expression of distinct DNA repair and neurodevelopmental factors. Mouse medulloblastomas expressing Pgbd5 have increased numbers of somatic structural DNA rearrangements, …

Temporal Considerations In Brain Metastases Radiation Therapy: The Intersection Of Chronobiology And Patient Profiles, Nicolas Nelson, Sara Burke, Louis Cappelli, Lauren Matlack, Alexandria Smith, Noelle Francois, Joseph Lombardo, Yash Shah, Kuang-Yi Wen, Ayesha A Shafi, Nicole Simone

Department of Radiation Oncology Faculty Papers

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival …

Investigating The Use Of Finerenone In Children With Chronic Kidney Disease And Proteinuria: Design Of The Fiona And Open-Label Extension Studies., Franz Schaefer, Giovanni Montini, Hee Gyung Kang, Johan Vande Walle, Joshua Zaritsky, Michiel F. Schreuder, Mieczyslaw Litwin, Andrea Scalise, Helen Scott, James Potts, Pablo Iveli, Stefanie Breitenstein, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.

OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that …

Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …

If1 Promotes Cellular Proliferation And Inhibits Oxidative Phosphorylation In Mouse Embryonic Fibroblasts Under Normoxia And Hypoxia, Lothar Lauterboeck, Sung Wook Kang, Donnell White, Rong Bao, Parnia Mobasheran, Qinglin Yang

School of Graduate Studies Faculty Publications

ATP synthase inhibitory factor subunit 1 (IF1) is an inhibitory subunit of mitochondrial ATP synthase, playing a crucial role in regulating mitochondrial respiration and energetics. It is well-established that IF1 interacts with the F1 sector of ATP synthase to inhibit the reversal rotation and, thus, ATP hydrolysis. Recent evidence supports that IF1 also inhibits forward rotation or the ATP synthesis activity. Adding to the complexity, IF1 may also facilitate mitophagy and cristae formation. The implications of these complex actions of IF1 for cellular function remain obscure. In the present study, we found that IF1 expression was markedly upregulated in hypoxic …

Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Anti-Inflammatory, Antipyretic, And Analgesic Potential Of Chitin And Chitosan Derived From Cockroaches (Periplaneta Americana) And Termites, Khushbakht Asad, Sumaira Shams, Eliana Ibáñez-Arancibia, Patricio R De Los Ríos-Escalante, Farhad Badshah, Farooq Ahmad, Muhammad Salman Khan, Asar Khan

Faculty, Staff and Student Publications

The chitin and chitosan biopolymers are extremely valuable because of their numerous industrial and pharmacological uses. Chitin and chitosan were extracted from the exoskeleton of Periplaneta americana (cockroaches) and termites using various acid and alkali techniques. The extraction process involves an initial demineralization step, during which integument dry powder was subjected to 500 mL (2.07 mol/L) of concentrated HCl at 100 degrees Celsius for 30 min, followed by meticulous rinsing with distilled water to restore the pH to its baseline. Deproteinization was conducted at 80 degrees Celsius using 500 mL (1 mol/L) of NaOH solution, which was repeated for 24 …