Biological Phenomena, Cell Phenomena, and Immunity | Open Access Articles

Mucosal Melanoma: Mechanisms Of Its Etiology, Progression, Resistance And Therapy, Sofie-Yasmin Hassan, Thomas W. Flanagan, Sarah-Lilly Hassan, Sybille Facca, Youssef Haikel, Mohamed Hassan

School of Graduate Studies Faculty Publications

Mucosal melanoma (MM) is a rare, aggressive cancer whose incidence has increased continuously over the years. This subtype of melanoma arises from melanocytes on hairless surfaces, typically in the respiratory tract, gastrointestinal (GI) tract, and urogenital tract. The most common sites of occurrence include the head and neck, the anorectal region, and the vulvovaginal region, while the rare sites of MM are the urinary tract and the upper and lower GI tract, including the esophagus, duodenum and the gallbladder. MM arises in melanocytes of the ectodermal mucosa that originate from neural crest cells and migrate through embryonic mesenchyme to their …

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Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

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Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels …

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Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …

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Exploring Cisd1 As A Multifaceted Biomarker In Cancer: Implications For Diagnosis, Prognosis, And Immunotherapeutic Response, Caiyue Li, Zhipin Liang, Gabrielle Vontz, Connor Kent, Wenbo Ma, Lei Liu, Riya Dahal, Jovanny Zabaleta, Guoshuai Cai, Jia Zhou, Huangen Ding, Qiang Shen

School of Graduate Studies Faculty Publications

CISD1, an outer mitochondrial membrane iron-sulfur cluster protein, regulates intracellular iron levels, oxidative stress, and mitochondrial dynamics, playing critical roles in cellular bioenergetics and redox homeostasis. Although CISD1 has been identified as a prognostic biomarker in specific cancers, its broader implications in tumorigenesis, cancer progression, and immunotherapy remain unclear. Given the heterogeneity of cancer and the need for robust biomarkers across cancers, this study conducts the first comprehensive pan-cancer analysis of CISD1 by evaluating its roles in cancer and treatment. We obtained and analyzed data from databases including TCGA, GTEx, THPA, GEPIA2.0, SangerBox, cBioPortal, TIMER2.0, CAMOIP, DAVID, SRPLOT, and TISIDB. …

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The Bone Marrow Endothelial Progenitor Cell Response To Septic Infection, Xin Shi, Kevin J. Simms, Thomas J. Ewing, Yuan-Ping Lin, Yi-Ling Chen, John N. Melvan, Robert W. Siggins, Ping Zhang

School of Graduate Studies Faculty Publications

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of . For experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)stem cell factor receptor (c-kit)stem cell antigen-1 (Sca-1), linc-kit, and lin cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of …

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Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana

School of Graduate Studies Faculty Publications

Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques. Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 …

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Dynamics Of Serum-Neutralizing Antibody Responses In Vaccinees Through Multiple Doses Of The Bnt162b2 Vaccine, Jared Sheehan, Caleb M. Ardizzone, Mayank Khanna, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 naïve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and …

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In Vivo Treatment With Insulin-Like Growth Factor 1 Reduces Ccr5 Expression On Vaccine-Induced Activated Cd4+ T-Cells, Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolò Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva De Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N’Guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini

School of Graduate Studies Faculty Publications

At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and …

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High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

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Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …

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Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …

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Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H. Elnaggar, Victoria O. Huynh, Daniel Lin, R. Tyler Hillman, Chike O. Abana, Molly B. El Alam, Katarina C. Tomasic, Tatiana V. Karpinets, Ramez Kouzy, Jae L. Phan, Jennifer Wargo, Emma B. Holliday, Prajnan Das, Melissa P. Mezzari, Nadim J. Ajami, Erica J. Lynn, Bruce D. Minsky, Van K. Morris, Andrea Milbourne, Craig A. Messick, Ann H. Klopp, P. Andrew Futreal, Cullen M. Taniguchi, Kathleen M. Schmeler, Lauren E. Colbert

School of Graduate Studies Faculty Publications

Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

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Full-Text Articles in Biological Phenomena, Cell Phenomena, and Immunity

Mucosal Melanoma: Mechanisms Of Its Etiology, Progression, Resistance And Therapy, Sofie-Yasmin Hassan, Thomas W. Flanagan, Sarah-Lilly Hassan, Sybille Facca, Youssef Haikel, Mohamed Hassan

School of Graduate Studies Faculty Publications

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications

Exploring Cisd1 As A Multifaceted Biomarker In Cancer: Implications For Diagnosis, Prognosis, And Immunotherapeutic Response, Caiyue Li, Zhipin Liang, Gabrielle Vontz, Connor Kent, Wenbo Ma, Lei Liu, Riya Dahal, Jovanny Zabaleta, Guoshuai Cai, Jia Zhou, Huangen Ding, Qiang Shen

School of Graduate Studies Faculty Publications

The Bone Marrow Endothelial Progenitor Cell Response To Septic Infection, Xin Shi, Kevin J. Simms, Thomas J. Ewing, Yuan-Ping Lin, Yi-Ling Chen, John N. Melvan, Robert W. Siggins, Ping Zhang

School of Graduate Studies Faculty Publications

Sutterella And Its Metabolic Pathways Positively Correlate With Vaccine-Elicited Antibody Responses In Infant Rhesus Macaques, Danting Jiang, Ria Goswami, Maria Dennis, Holly Heimsath, Pamela A. Kozlowski, Amir Ardeshir, Koen K.A. Van Rompay, Kristina De Paris, Sallie R. Permar, Neeraj K. Surana

School of Graduate Studies Faculty Publications

Dynamics Of Serum-Neutralizing Antibody Responses In Vaccinees Through Multiple Doses Of The Bnt162b2 Vaccine, Jared Sheehan, Caleb M. Ardizzone, Mayank Khanna, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications