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Articles 2521 - 2550 of 14290

Full-Text Articles in Medical Specialties

Interobserver Variability Regarding Adequacy Of Oropharyngeal Exposure For Transoral Robotic Surgery May Necessitate Staging Endoscopy: Evaluating Tors Exposure, Colleen Schinderle, Kevin J. Carlson, Reem Sharaf Alddin, Jeffery J. Houlton, Matthew J. Bak, Daniel W. Karakla, Jonathan R. Mark Jan 2025

Interobserver Variability Regarding Adequacy Of Oropharyngeal Exposure For Transoral Robotic Surgery May Necessitate Staging Endoscopy: Evaluating Tors Exposure, Colleen Schinderle, Kevin J. Carlson, Reem Sharaf Alddin, Jeffery J. Houlton, Matthew J. Bak, Daniel W. Karakla, Jonathan R. Mark

Department of Otolaryngology (ENT) Faculty Publications

[First paragraph] Transoral robotic surgery (TORS) for the treatment of oropharyngeal cancer has become centered at tertiary referral centers. To avoid treatment delays or multiple anesthetics, the need for repeat operative endoscopy may be questioned when the diagnosis has been made at an outside institution. However, inadequate visualization of relevant anatomy can preclude TORS candidacy and may lead to procedure abortion or conversion to an open technique.²,³ To evaluate this dilemma, we explored the ability to assess oropharyngeal exposure for TORS candidacy via operative endoscopic photo-documentation.


Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning Jan 2025

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …


Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior Jan 2025

Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior

Faculty, Staff and Student Publications

No abstract provided.


Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran Jan 2025

Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

Background: Transcranial direct current stimulation is a non-invasive neuromodulation technique with emerging therapeutic potential in neurodevelopmental conditions. While childhood-onset stroke survivors frequently experience long-term motor impairment, there are very few studies examining the safety and feasibility of transcranial direct current stimulation in this population.

Objective: To evaluate the safety, feasibility, and tolerability of bihemispheric transcranial direct current stimulation paired with occupational therapy in children and adolescents with chronic hemiparesis following childhood-onset arterial ischemic stroke or intracranial hemorrhage.

Methods: In this single-arm, open-label pilot study, five participants aged 6-19 years of age received five daily sessions of transcranial direct current stimulation …


Smoking Habit And Long-Term Colorectal Cancer Incidence By Exome-Wide Mutational And Neoantigen Loads: Evidence Based On The Prospective Cohort Incident-Tumour Biobank Method, Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino Jan 2025

Smoking Habit And Long-Term Colorectal Cancer Incidence By Exome-Wide Mutational And Neoantigen Loads: Evidence Based On The Prospective Cohort Incident-Tumour Biobank Method, Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino

Faculty, Staff and Student Publications

Objective: To test the hypothesis that the association of smoking with long-term colorectal cancer incidence may be stronger for tumours with higher mutational and neoantigen loads.

Methods and analysis: In the Nurses' Health Study (1980-2012) and the Health Professionals Follow-up Study (1986-2012), our novel prospective cohort incident-tumour biobank method (PCIBM) used 3053 incident colorectal carcinoma cases including 752 cases with whole-exome sequencing data. Using the multivariable duplication-method Cox regression model with the inverse probability weighting to adjust for the selection bias due to tissue availability, we assessed a differential association of cigarette smoking with colorectal carcinoma incidence by an exome-wide …


Anaplastic Large Cell Lymphoma In Children And Adolescents, Eric J. Lowe, Wilhelm Woessmann Jan 2025

Anaplastic Large Cell Lymphoma In Children And Adolescents, Eric J. Lowe, Wilhelm Woessmann

Department of Pediatrics Faculty Publications

Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) accounts for >95% of ALCL cases in children and adolescents. The first description of ALCL as a CD30-positive lymphoma in 1985 was followed by the detection of chromosomal translocations involving the ALK gene at chromosome 2p23. The pathogenesis of ALK-positive ALCL is based on signalling from the constitutive active ALK kinase. The clinical characteristics, therapy regimens and outcome data were reported in the 1990s and 2000s. Different chemotherapy regimens led to astonishingly similar long-term event-free survival rates of 70%, independent of the drugs, doses and duration of therapy. Additionally, patients with relapsed …


Enhanced Anticancer Activity Of Novel Pyrimidine Nucleoside Analog In Pancreatic Cancer, Raviteja Bulusu, Joy Okoro, Esther Frimpong, Sunil Krishnan, Saunjoo Yoon, Bo Han, Xue Zhu, Edward Agyare Jan 2025

Enhanced Anticancer Activity Of Novel Pyrimidine Nucleoside Analog In Pancreatic Cancer, Raviteja Bulusu, Joy Okoro, Esther Frimpong, Sunil Krishnan, Saunjoo Yoon, Bo Han, Xue Zhu, Edward Agyare

The Brown Foundation: Institute of Molecular Medicine

This study explores the synthesis, characterization, and therapeutic efficacy of AGY1, AGY2, AGY3, AGY4, and AGY5, which are novel 5-FU analogs designed to improve metabolic stability, prolong half-life, and anti-tumor activity against pancreatic cancer. The 5-FU molecule was chemically modified to bypass dihydropyrimidine dehydrogenase (DPD)-mediated inactivation, enhancing drug retention and increasing lipophilicity for improved cellular uptake. The analog cytotoxic activity was evaluated in 2D monolayer cultures and 3D pancreatic cancer spheroids and organoid models derived from MiaPaCa-2 and PANC-1 cells to simulate a more complex tumor environment. In the 2D model, AGY1, AGY2, AGY3, AGY4, and AGY5 displayed significantly higher …


Extension For Community Healthcare Outcomes-Palliative Care In Africa And Quality Of Life, Symptoms, Patient Experience, And Caregiver Distress Among Patients With Cancer, Sriram Yennurajalingam, Olaitan Soyannwo, John Weru, Edwina Beryl, Henriette Burger, Esther Nafulah, Oladayo Aikomo, Adeniyi Adenipekun, Irene Botchway, Mary Ocansey Jan 2025

Extension For Community Healthcare Outcomes-Palliative Care In Africa And Quality Of Life, Symptoms, Patient Experience, And Caregiver Distress Among Patients With Cancer, Sriram Yennurajalingam, Olaitan Soyannwo, John Weru, Edwina Beryl, Henriette Burger, Esther Nafulah, Oladayo Aikomo, Adeniyi Adenipekun, Irene Botchway, Mary Ocansey

Haematology and Oncology, East Africa

Purpose: In this study, we aimed to evaluate the association between the Extension for Community Healthcare Outcomes-Palliative Care (ECHO-PC; ECHO Model–Based comprehensive educational and telementoring intervention) for health care professionals (HCPs) and change in patient-reported quality-of-life (QOL; Functional Assessment of Cancer Therapy-General [FACT-G]) among patients with advanced cancer. We also examined the association between ECHO-PC and changes in symptom distress (Edmonton Symptom Assessment Scale [ESAS]), patient experience and satisfaction, and caregiver distress scores.

Methods: ECHO-PC Clinic sessions were conducted twice a month for 1 year by an interdisciplinary team of PC clinicians at the MD Anderson Cancer Center, with participation …


Risk And Prognosis Of Hepatocellular Carcinoma In Mexican Americans With Type 2 Diabetes Mellitus, Rikita I Hatia, Lu-Yu Hwang, Ruosha Li, Catherine Troisi, Prasun K Jalal, Christopher I Amos, Henry F Gomez, Yun Shin Chun, Asif Rashid, Ahmed O Kaseb, Paul A Scheet, Manal M Hassan Jan 2025

Risk And Prognosis Of Hepatocellular Carcinoma In Mexican Americans With Type 2 Diabetes Mellitus, Rikita I Hatia, Lu-Yu Hwang, Ruosha Li, Catherine Troisi, Prasun K Jalal, Christopher I Amos, Henry F Gomez, Yun Shin Chun, Asif Rashid, Ahmed O Kaseb, Paul A Scheet, Manal M Hassan

Faculty, Staff and Student Publications

INTRODUCTION: Hepatocellular carcinoma (HCC) disproportionately affects Hispanic persons with higher age-specific incidence and increased mortality rates compared to non-Hispanic Whites. These high rates of incidence and mortality may be explained by the variation in risk factors. Given the high prevalence of type 2 diabetes mellitus (DM) among the Hispanic population, we aimed to assess the risk and prognosis of HCC in Mexican Americans with type 2 DM with consideration of treatment for DM.

METHODS: A case-control study of 241 Mexican American HCC patients and 500 healthy controls in Texas was conducted. Multivariable logistic regression analysis was performed to determine the …


Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno Jan 2025

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno

School of Medical Diagnostics & Translational Sciences Publications

The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells …


Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse Jan 2025

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)4-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn2+ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …


Molecular Imaging Of Triple-Negative Breast Cancer: Characterization And Modulation Of The Tumor Microenvironment, Shannon E. Lynch Jan 2025

Molecular Imaging Of Triple-Negative Breast Cancer: Characterization And Modulation Of The Tumor Microenvironment, Shannon E. Lynch

All ETDs from UAB

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subset of breast cancer which currently has no targeted therapies available due to lack of molecular therapeutic targets. Importantly, various radiopharmaceuticals can be imaged via positron emission tomography (PET) to quantify cellular and molecular features of the tumor microenvironment including glucose metabolism, receptor status, and immune activation. Somatostatin receptor subtype 2 (SSTR2) is G-protein coupled receptor overexpressed in neuroendocrine tumors (NETs) which can be imaged and targeted for theranostics via FDA-approved radiotherapy. SSTR2 expression is increased in hormone positive breast cancer but is expressed at low or variable levels in TNBC. However, …


Evaluating Multiparametric Imaging Biomarkers For Guiding Targeted Therapies In Her2+ Breast Cancer, Ameer Mansur Jan 2025

Evaluating Multiparametric Imaging Biomarkers For Guiding Targeted Therapies In Her2+ Breast Cancer, Ameer Mansur

All ETDs from UAB

Human epidermal growth factor receptor 2 positive (HER2+) breast cancer is a biologically diverse disease, in which intratumoral heterogeneity plays a significant role in tumor progression. Advanced medical imaging and image processing techniques offer the potential to noninvasively characterize the underlying intratumoral biology. Capturing these complex changes can allow for assessing therapeutic response and eventually guiding personalized therapeutic strategies. This work evaluates single and multiparametric imaging biomarkers to characterize tumor biology, identify treatment-induced changes, and predict response to targeted therapies. First, the utility of 3’-Deoxy-3’-[18F]Fluorothymidine positron emission tomography ([18F]FLT-PET) was assessed as a biomarker of proliferation for monitoring response to …


Electrochemical Strategies For Microrna Quantification Leveraging Amplification And Nanomaterials: A Review, Alexander Hunt, Gymama Slaughter Jan 2025

Electrochemical Strategies For Microrna Quantification Leveraging Amplification And Nanomaterials: A Review, Alexander Hunt, Gymama Slaughter

Center for Bioelectronics Publications

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have emerged as critical biomarkers in various diseases, including cancer. Their stability in bodily fluids and role as oncogenes or tumor suppressors make them attractive targets for non-invasive diagnostics. However, conventional detection methods, such as Northern blotting, RT-PCR, and microarrays, are limited by low sensitivity, lengthy protocols, and limited specificity. Electrochemical biosensors offer a promising alternative, providing high sensitivity, rapid response times, portability, and cost-effectiveness. These biosensors translate miRNA hybridization events into quantifiable electrochemical signals, often leveraging redox-active labels, mediators, or intercalators. Recent advancements in nanomaterials and signal amplification …


Biomedical Mxene-Polymer Nanocomposites: Advancing Photothermal Therapy, Antibacterial Action, And Smart Drug Delivery: A Review, Ali Mohammad Amani, Lobat Tayebi, Ehsan Vafa, Mohammad Javad Azizli, Milad Abbasi, Ahmad Vaez, Hesam Kamyab, Daniel Simancas-Racines, Shreeshivadasan Chelliapan Jan 2025

Biomedical Mxene-Polymer Nanocomposites: Advancing Photothermal Therapy, Antibacterial Action, And Smart Drug Delivery: A Review, Ali Mohammad Amani, Lobat Tayebi, Ehsan Vafa, Mohammad Javad Azizli, Milad Abbasi, Ahmad Vaez, Hesam Kamyab, Daniel Simancas-Racines, Shreeshivadasan Chelliapan

Electrical & Computer Engineering Faculty Publications

MXenes are hydrophilic, conductive, tunable, and biocompatible two-dimensional ceramic materials prepared by etching the 'A' layer from their precursor MAX phases. Although MXenes show exceptional promise in photothermal therapy, biosensing, and regenerative medicine, they face challenges such as oxidative instability in physiological environments, limited drug-loading capacity, and unpredictable immune responses. To address these limitations, MXene/polymer nanocomposites incorporating both synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and polylactic-co-glycolic acid (PLGA)) and natural biopolymers (e.g., cellulose nanofiber, gelatin, chitosan, hyaluronic acid, and soybean phospholipids) have been developed. These composites enhance functionality for biomedical applications such as photothermal cancer …


Targeted Therapies And Parpi Therapy Response Following Ici Therapy Failure In Advanced Melanoma, George Nassief, Renee Morecroft, Jordan Phillipps, David Chen, George Ansstas Jan 2025

Targeted Therapies And Parpi Therapy Response Following Ici Therapy Failure In Advanced Melanoma, George Nassief, Renee Morecroft, Jordan Phillipps, David Chen, George Ansstas

South Atlantic Division GME Research Day 2025

No abstract provided.


Developing Chemically Defined Serum-Free Medium For Leukemic Blast And Stem Cell Expansion, Carmen Eva Finley Jan 2025

Developing Chemically Defined Serum-Free Medium For Leukemic Blast And Stem Cell Expansion, Carmen Eva Finley

Dissertations

The relapse and chemotherapy resistance are the major challenges of acute myeloid leukemia (AML) treatment, driven by a rare population of leukemia stem cells (LSCs). LSCs are unique types of cells which evade standard chemotherapies and can regenerate AML post-treatment. Targeting LSC therapy remains limited, in part due to the lack of reliable in vitro AML culture systems to grow LSCs for drug discovery. This study aimed to engineer a chemically defined, serum-free 2D in vitro culture condition that supports either the expansion of leukemic blasts (LBs) or primary human LSCs by optimizing current protocols for hematopoietic stem cells (HSCs) …


Investigating The Role Of Rps3 In The Homologous Recombination Dna Repair Pathway, Jerome Robert Dorsey Jan 2025

Investigating The Role Of Rps3 In The Homologous Recombination Dna Repair Pathway, Jerome Robert Dorsey

Theses and Dissertations

Ribosomal proteins have been demonstrated to perform extra-ribosomal functions beyond protein synthesis, including roles in cell signaling, transcription regulation, apoptosis, and DNA repair. Ribosomal protein S3 (RPS3), in particular, has been implicated in DNA repair and apoptosis pathways, suggesting a critical role in maintaining genomic stability. However, the specific mechanisms involving RPS3 are still unknown, particularly in the context of double-stranded break (DSB) repair. DSBs are among the most severe types of DNA damage, often resulting in chromosomal instability or cell death if not properly repaired. Nonhomologous End Joining (NHEJ) and Homologous Recombination (HR) are the two primary DNA repair …


A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza Jan 2025

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …


Treatment Of Myocardial Infiltration Of Hodgkins Lymphoma: A Catch-22, Jennifer Priessnitz, Erin Biringen, Fadi Khoury, Christina Bergin Jan 2025

Treatment Of Myocardial Infiltration Of Hodgkins Lymphoma: A Catch-22, Jennifer Priessnitz, Erin Biringen, Fadi Khoury, Christina Bergin

Department of Medicine Faculty Publications

Background: Cardiac sequelae in Hodgkin Lymphoma (HL) can manifest as involvement of the heart and pericardium. Direct cardiac involvement is rare, and myocardial infiltration is distinctly unusual.¹ When it does occur, it is often a late manifestation of lymphoma, with a median onset of 20 months after initial diagnosis, and it is usually associated with advanced-stage disease.²

Case: A 34-year-old male was diagnosed with classic HL by lymph node biopsy. During his hospitalization, the patient remained in sinus tachycardia with heart rate up to 150 with no dysrhythmias. Transthoracic echocardiogram (TTE) revealed a reduced ejection fraction (EF) of 36% concerning …


Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen Jan 2025

Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

Ionizing radiation (IR) poses a dual challenge in medicine; while essential for cancer therapy, it inflicts collateral damage to normal tissues, particularly the gastrointestinal (GI) tract. High-dose IR triggers acute radiation syndrome (ARS), characterized by crypt stem cell depletion, mucosal barrier disruption, inflammation, and potential progression to fibrosis and secondary malignancy. Emerging evidence identifies the epithelial kinase doublecortin-like kinase 1 (DCLK1)—highly expressed in GI tuft cells and cancer stem-like cells—as a master regulator of post-IR responses. DCLK1 integrates DNA repair (via p53/ATM), and survival signaling (via NF-κB, TGF-β, and MAPK) to promote epithelial regeneration, yet these same mechanisms contribute to …


Oral Microbiome And Inflammatory Bowel Disease: New Understanding And Call To Action, Michael Saadeh, Sydney Donohue, Shaina Ailawadi, Gordon Hong, David A. Johnson Jan 2025

Oral Microbiome And Inflammatory Bowel Disease: New Understanding And Call To Action, Michael Saadeh, Sydney Donohue, Shaina Ailawadi, Gordon Hong, David A. Johnson

Department of Medicine Faculty Publications

The oral microbiome is the second largest microbial community in the human body after the gut microbiome. It includes an array of fungi, bacteria, amoebae, flagellates, archaea, and viruses, all of which are potential pathogens. This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs. Although conventional thought is this is primarily in terms of oral health issues, such as dental caries and gingival disease. The systemic effects of the oral microbiome however, are relevant to both gastrointestinal (GI) disease and non-GI disease. These systemic risks occur for several reasons, including upregulation …


Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai Jan 2025

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …


A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen Jan 2025

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …


Micro/Nanoplastics And Cancer: Focus On Gastrointestinal Malignancies - A Narrative Review, Sana Rabeeah, Priyata Dutta, Ahmad Mahdi, Alejandra Vargas, Edward C. Oldfield, David A. Johnson Jan 2025

Micro/Nanoplastics And Cancer: Focus On Gastrointestinal Malignancies - A Narrative Review, Sana Rabeeah, Priyata Dutta, Ahmad Mahdi, Alejandra Vargas, Edward C. Oldfield, David A. Johnson

Department of Medicine Faculty Publications

Micro- and nanoplastics (MNPs) are plastic particles smaller than 5 mm and 1 μm, respectively, and are emerging environmental pollutants with growing implications for human health. These particles stem from either 'primary sources', such as intentionally manufactured microbeads and industrial abrasives, or 'secondary sources', where larger plastic items break down into smaller fragments over time. Human exposure primarily occurs through ingestion and inhalation, with contaminated seafood and plastic-laden food packaging representing key routes of entry. Once ingested, MNPs can cross the intestinal barrier, accumulate in gastrointestinal (GI) tissues, and trigger biological responses. Mechanistic studies reveal that MNPs induce oxidative stress, …


Novel Micro-And Nanoformulations Of Paclitaxel For Targeting Metastatic Breast, Non-Small Cell Lung, And Pancreatic Cancers, Lobat Tayebi, Mehran Alavi Jan 2025

Novel Micro-And Nanoformulations Of Paclitaxel For Targeting Metastatic Breast, Non-Small Cell Lung, And Pancreatic Cancers, Lobat Tayebi, Mehran Alavi

Electrical & Computer Engineering Faculty Publications

Nonlinear pharmacokinetics resulting from high lipophilic and low oral bioavailability, and hypersensitivity reactions and hyperlipidemia caused by formulation by Cremophor EL have limited clinical effectiveness of paclitaxel (Taxol). In this way, there is the critical necessity of innovative drug delivery systems (DDSs) to mitigate severe side effects and overcome clinical limitations of paclitaxel. In recent years, various micro- and nanoformulations, specifically polymeric nanoparticles (NPs) and lipid NPs, have been presented and approved by the Food and Drug Administration (FDA). In addition, other nanoformulations, such as polymeric nanoparticles (NPs), micelles, liposomes, and mesoporous silica nanoparticles, have shown promising results in vitro …


Upregulation Of Delta Opioid Receptor By Meningeal Interleukin-10 Prevents Relapsing Pain, Kufreobong E Inyang, Jaewon Sim, Kimberly B Clark, Matan Geron, Karli Monahan, Christine Evans, Patrick O'Connell, Sophie Laumet, Bo Peng, Jiacheng Ma, Cobi J Heijnen, Robert Dantzer, Grégory Scherrer, Annemieke Kavelaars, Matthew Bernard, Yasser A Aldhamen, Joseph K Folger, Alexis Bavencoffe, Geoffroy Laumet Jan 2025

Upregulation Of Delta Opioid Receptor By Meningeal Interleukin-10 Prevents Relapsing Pain, Kufreobong E Inyang, Jaewon Sim, Kimberly B Clark, Matan Geron, Karli Monahan, Christine Evans, Patrick O'Connell, Sophie Laumet, Bo Peng, Jiacheng Ma, Cobi J Heijnen, Robert Dantzer, Grégory Scherrer, Annemieke Kavelaars, Matthew Bernard, Yasser A Aldhamen, Joseph K Folger, Alexis Bavencoffe, Geoffroy Laumet

Faculty, Staff and Student Publications

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological …


Neutrophils Unveiled In Chronic Lymphocytic Leukemia, Sheighlah Mcmanus, Priyanka Khare, Maria Teresa S Bertilaccio Jan 2025

Neutrophils Unveiled In Chronic Lymphocytic Leukemia, Sheighlah Mcmanus, Priyanka Khare, Maria Teresa S Bertilaccio

Faculty, Staff and Student Publications

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strategies to manage therapy-induced immune dysfunction. This review also provides detailed information about the interactions between neutrophils and other immune elements …


Microbial Imprints On Colorectal Cancer: The Epigenetic Silencing Of Phlpp1 As A Prognostic Nexus, Xiangsheng Huang, Faraz Bishehsari Jan 2025

Microbial Imprints On Colorectal Cancer: The Epigenetic Silencing Of Phlpp1 As A Prognostic Nexus, Xiangsheng Huang, Faraz Bishehsari

Faculty, Staff and Student Publications

No abstract provided.


Editorial: Protein Regulation By Lipids, Mikhail V Bogdanov, Elena G Govorunova Jan 2025

Editorial: Protein Regulation By Lipids, Mikhail V Bogdanov, Elena G Govorunova

Faculty, Staff and Student Publications

No abstract provided.