Medical Specialties Commons^™

Zyxin Inhibits The Epithelial-Mesenchymal Transition Process In Gastric Cancer By Upregulating Sirt1, Jing Lou, Sha Geng, Wei He, Song-Bai Liu, Xinghong Shi, Ying Chang, Shiyuan Han, Panting Qian, Hesham M Amin, Yao-Hua Song, Yangxin Li, Jin Zhou

Faculty, Staff and Student Publications

Tumor development relies on the stemness of cancer stem cells, which is regulated by environmental cues. Previous studies have shown that zyxin can inhibit the expression of genes for embryonic stem cell status. In the present study, the expression levels of zyxin protein in cancer tissues and adjacent noncancerous tissues from 73 gastric cancer patients with different clinical stages were analyzed by Western blot. We showed that the relative expression levels of zyxin in gastric cancer tissues (cancer tissues/adjacent tissues) were significantly downregulated in advanced clinical stages. Overexpression of zyxin inhibited the stemness and epithelial-mesenchymal transition (EMT) processes in gastric …

Evaluation Of The Natural History Of Disease By Combining Incident And Prevalent Cohorts: Application To The Nun Study, Daewoo Pak, Jing Ning, Richard J Kryscio, Yu Shen

Faculty, Staff and Student Publications

The Nun study is a well-known longitudinal epidemiology study of aging and dementia that recruited elderly nuns who were not yet diagnosed with dementia (i.e., incident cohort) and who had dementia prior to entry (i.e., prevalent cohort). In such a natural history of disease study, multistate modeling of the combined data from both incident and prevalent cohorts is desirable to improve the efficiency of inference. While important, the multistate modeling approaches for the combined data have been scarcely used in practice because prevalent samples do not provide the exact date of disease onset and do not represent the target population …

A Self-Configuring Deep Learning Network For Segmentation Of Temporal Bone Anatomy In Cone-Beam Ct Imaging, Andy S Ding, Alexander Lu, Zhaoshuo Li, Manish Sahu, Deepa Galaiya, Jeffrey H Siewerdsen, Mathias Unberath, Russell H Taylor, Francis X Creighton

Faculty, Staff and Student Publications

OBJECTIVE: Preoperative planning for otologic or neurotologic procedures often requires manual segmentation of relevant structures, which can be tedious and time-consuming. Automated methods for segmenting multiple geometrically complex structures can not only streamline preoperative planning but also augment minimally invasive and/or robot-assisted procedures in this space. This study evaluates a state-of-the-art deep learning pipeline for semantic segmentation of temporal bone anatomy.

STUDY DESIGN: A descriptive study of a segmentation network.

SETTING: Academic institution.

METHODS: A total of 15 high-resolution cone-beam temporal bone computed tomography (CT) data sets were included in this study. All images were co-registered, with relevant anatomical structures …

Garetosmab In Fibrodysplasia Ossificans Progressiva: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Maja Di Rocco, Eduardo Forleo-Neto, Robert J Pignolo, Richard Keen, Philippe Orcel, Thomas Funck-Brentano, Christian Roux, Sami Kolta, Annalisa Madeo, Judith S Bubbear, Jacek Tabarkiewicz, Małgorzata Szczepanek, Javier Bachiller-Corral, Angela M Cheung, Kathryn M Dahir, Esmée Botman, Pieter G Raijmakers, Mona Al Mukaddam, Lianne Tile, Cynthia Portal-Celhay, Neena Sarkar, Peijie Hou, Bret J Musser, Anita Boyapati, Kusha Mohammadi, Scott J Mellis, Andrew J Rankin, Aris N Economides, Dinko Gonzalez Trotter, Gary A Herman, Sarah J O'Meara, Richard Delgizzi, David M Weinreich, George D Yancopoulos, E Marelise W Eekhoff, Frederick S Kaplan

Faculty, Staff and Student Publications

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths …

Young-Onset Rectal Cancer: Unique Tumoral Microbiome And Correlation With Response To Neoadjuvant Therapy, Michael G White, Ashish Damania, Jumanah Alshenaifi, Pranoti Sahasrabhojane, Oliver Peacock, Jillian Losh, Matthew C Wong, Zuzana Lutter-Berkova, George J Chang, Andrew Futreal, Jennifer A Wargo, Nadim J Ajami, Scott Kopetz, Y Nancy You

Faculty, Staff and Student Publications

OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

BACKGROUND: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.

METHODS: YORC (old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to …

Peripheral Levels Of The Brain-Derived Neurotrophic Factor In Coronary Artery Disease: A Systematic Review And Meta-Analysis, Parnian Shobeiri, Amir Hossein Behnoush, Amirmohammad Khalaji, Antonio Lucio Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls.

METHODS: We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted …

Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity, Thomas B K Watkins, Emma C Colliver, Matthew R Huska, Tom L Kaufmann, Emilia L Lim, Cody B Duncan, Kerstin Haase, Peter Van Loo, Charles Swanton, Nicholas Mcgranahan, Roland F Schwarz

Faculty, Staff and Student Publications

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient's disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase's ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.

Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences In Children And Adults, Jamie Amemiya, Gail D Heyman, Caren M Walker

Faculty, Staff and Student Publications

People often hear stories about individuals who persist to overcome their constraints. While these stories can be motivating, emphasizing others’ persistence may promote unwarranted judgments about constrained individuals who do not persist. Using a developmental social inference task (Study 1a: n = 124 U.S. children, 5 to 12 years of age; Study 1b [n = 135] and Study 2 [n = 120]: U.S. adults), the present research tested whether persistence stories lead people to infer that a constrained individual who does not persist, and instead accepts the lower-quality option that is available to them, prefers it over a …

Prevalence Of Pituitary Hormone Dysfunction Following Radiotherapy For Sinonasal And Nasopharyngeal Malignancies, Kevin J Contrera, Jack Phan, Steven G Waguespack, Mohammed Aldehaim, Xin Wang, Tze Yee Lim, Dianna B Roberts, C David Fuller, Michael T Spiotto, Shaan M Raza, Franco Demonte, Ehab Y Hanna, Shirley Y Su

Faculty, Staff and Student Publications

BACKGROUND: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation.

METHODS: Cross-sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated.

RESULTS: Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P …

Single-Agent Lenalidomide Maintenance After Upfront Autologous Stem Cell Transplant For Newly Diagnosed Multiple Myeloma: The Md Anderson Experience, Oren Pasvolsky, Denái R Milton, Adeel Masood, Sophiya S Sami, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Arsalan Saeed, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The optimal duration of lenalidomide (Len) maintenance for patients with multiple myeloma (MM) after autologous stem cell transplantation (autoHCT) is unknown. We conducted a retrospective single-center analysis of adult MM patients that received upfront autoHCT between 2005 and 2021, followed by single-agent Len maintenance. A total of 1167 patients were included with a median age of 61.4 (range 25.4-82.3) years, and high-risk chromosomal abnormalities in 19%. Median duration of maintenance was 22.3 (range 0.03-139.6) months. After a median follow-up of 47.9 (range 2.9-171.7) months, median PFS and OS for the entire cohort were 56.6 (95% CI 48.2-61.4) months and 111.3 …

A Machine Learning Approach That Measures Ph Using Acidocest Mri Of Iopamidol, Tianzhe Li, Julio Cárdenas-Rodríguez, Priya N Trakru, Mark D Pagel

Faculty, Staff and Student Publications

Tumor acidosis is an important biomarker for aggressive tumors, and extracellular pH (pHe) of the tumor microenvironment can be used to predict and evaluate tumor responses to chemotherapy and immunotherapy. AcidoCEST MRI measures tumor pHe by exploiting the pH-dependent chemical exchange saturation transfer (CEST) effect of iopamidol, an exogenous CT agent repurposed for CEST MRI. However, all pH fitting methodologies for acidoCEST MRI data have limitations. Herein we present results of the application of machine learning for extracting pH values from CEST Z-spectra of iopamidol. We acquired 36,000 experimental CEST spectra from 200 phantoms of iopamidol prepared at five concentrations, …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour

Biomedical Engineering Theses & Dissertations

The use of nanosecond pulsed electric fields (nsPEF) has emerged as a promising area of research with vast implications across various scientific disciplines. The ability to generate ultra-short, high-voltage electric pulses has paved the way for numerous applications, ranging from fundamental investigations of biological phenomena to the development of innovative medical therapies. The aim of this thesis is to highlight the importance of nsPEF in two critical areas: 1) Understanding the impact of subtle postpulse waveforms through a comprehensive analysis of two common pulse generators and 2) using this knowledge to advance melanoma treatment by enhancing the therapeutic effect of …

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

A Blunted Th17 Cytokine Signature In Women With Mild Cognitive Impairment: Insights From Inflammatory Profiling Of A Community-Based Cohort Of Older Adults, Adam D. Bachstetter, Jenny Lutshumba, Edric D. Winford, Erin L. Abner, Barbra J. Martin, Jordan P. Harp, Linda J. Van Eldik, Frederick A. Schmitt, Donna M. Wilcock, Ann M. Stowe, Gregory A. Jicha, Barbara S. Nikolajczyk

Markey Cancer Center Faculty Publications

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells …

Control Of Cd4+ T Cells To Restrain Inflammatory Diseases Via Eukaryotic Elongation Factor 2 Kinase, Hao-Yun Peng, Liqing Wang, Jugal Kishore Das, Anil Kumar, Darby J. Ballard, Yijie Ren, Xiaofeng Xiong, Paul De Figueiredo, Jin-Ming Yang, Jianxun Song

Markey Cancer Center Faculty Publications

CD4+ T cells, particularly IL-17-secreting helper CD4+ T cells, play a central role in the inflammatory processes underlying autoimmune disorders. Eukaryotic Elongation Factor 2 Kinase (eEF2K) is pivotal in CD8+ T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension. However, its specific immunological role in CD4+ T cell activities and related inflammatory diseases remains elusive. Our investigation has uncovered that the deficiency of eEF2K disrupts the survival and proliferation of CD4+ T cells, impairs their ability to secrete cytokines. Notably, this dysregulation leads to heightened production of pro-inflammatory cytokine IL-17, fosters a pro-inflammatory microenvironment …

Copy Number Variation That Influences The Ionizing Radiation Sensitivity Of Oral Squamous Cell Carcinoma, Tadahide Izumi, Piotr G. Rychahou, Li Chen, Molly H. Smith, Joseph Valentino

Markey Cancer Center Faculty Publications

Genome instability in cancer cells causes not only point mutations but also structural variations of the genome, including copy number variations (CNVs). It has recently been proposed that CNVs arise in cancer to adapt to a given microenvironment to survive. However, how CNV influences cellular resistance against ionizing radiation remains unknown. PRMT5 (protein arginine methyltransferase 5) and APE1 (apurinic/apyrimidinic endonuclease 1), which enhance repair of DNA double-strand breaks and oxidative DNA damage, are closely localized in the chromosome 14 of the human genome. In this study, the genomics data for the PRMT5 and APE1 genes, including their expression, CNVs, and …

Dense Granule Protein 3 Of Toxoplasma Gondii Plays A Crucial Role In The Capability Of The Tissue Cysts Of The Parasite To Persist In The Presence Of Anti-Cyst Cd8+ T Cells During The Chronic Stage Of Infection, Rajesh Mani, Mohamed H. Abdelaziz, Eri Ochiai, Qila Sa, Barbara A. Fox, David J. Bzik, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii establishes chronic infection by forming tissue cysts, and this chronic infection is one of the most common parasitic infections in humans. Our recent studies revealed that whereas CD8 + T cells of genetically resistant BALB/c mice have the capability to remove the tissue cysts of the parasite through their perforin-mediated activities, small portions of the cysts are capable of persisting in the presence of the anti-cyst CD8+ T cells. It is currently unknown how those small portions of the cysts resist or escape the T-cell immunity and persist in the hosts. In the present study, we discovered that …

Distinct Camp Signaling Microdomains Differentially Regulate Melanosomal Ph And Pigmentation, Maftuna Yusupova, Dalee Zhou, Jaewon You, Jeydi Gonzalez-Guzman, Megha B. Ghanta, Hong Pu, Zalfa Abdel-Malek, Qiuying Chen, Steven S. Gross, John August D'Orazio, Shosuke Ito, Kazumasa Wakamatsu, Melissa L. Harris, Jonathan H. Zippin

Markey Cancer Center Faculty Publications

cAMP signaling is a well-established regulator of melanin synthesis. Two distinct cAMP signaling pathways—the transmembrane adenylyl cyclase pathway, activated primarily by the MC1R, and the soluble adenylyl cyclase (sAC) pathway—affect melanin synthesis. The sAC pathway affects melanin synthesis by regulating melanosomal pH, and the MC1R pathway affects melanin synthesis by regulating gene expression and post-translational modifications. However, whether MC1R genotype affects melanosomal pH is poorly understood. We now report that loss of function MC1R does not affect melanosomal pH. Thus, sAC signaling appears to be the only cAMP signaling pathway that regulates melanosomal pH. We also addressed whether MC1R genotype …

Effects Of Interfraction Dose Variations Of Target And Organs At Risk On Clinical Outcomes In High Dose Rate Brachytherapy For Cervical Cancer, Brien Washington, Dennis C. Cheek, Denise Fabian, Mahesh R. Kudrimoti, Damodar Pokhrel, Chi Wang, Cameron Thayer-Freeman, Wei Luo

Markey Cancer Center Faculty Publications

Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely discussed in the literature. Our previous study found that IDVs followed a left-skewed distribution. The clinical effect of the IDVs in 100 cervical cancer HDR patients will be addressed in this paper. An in-house Monte Carlo (MC) program was used to simulate clinical outcomes by convolving published tumor dose response curves with IDV distributions. The optimal dose …

Elongation Of Very Long Chain Fatty Acids-3 (Elovl3) Is Activated By Zhx2 And Is A Regulator Of Cell Cycle Progression, Kate Townsend Creasy, Hui Ren, Jieyun Jiang, Martha L. Peterson, Brett T. Spear

Markey Cancer Center Faculty Publications

Zinc fingers and homeoboxes 2 (Zhx2) are transcriptional regulators of liver gene expression with key functions in embryonic development as well as tissue regeneration in response to damage and disease, presumably through its control of target genes. Previous microarray data suggested that elongation of very long chain fatty acids-3 (Elovl3), a member of the ELOVL family of enzymes that synthesize very long chain fatty acids (VLCFAs), is a putative Zhx2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids that are often dysregulated in diseases and regulate key cellular processes including proliferation. Since several previously identified Zhx2 …

Inhibition Of Mitochondrial Fission Activates Glycogen Synthesis To Support Cell Survival In Colon Cancer, Sumati Raj Hasani, Lyndsay E. A. Young, Warren Van Nort, Moumita Banerjee, Dylan R. Rivas, Jinhwan Kim, Xiaopeng Xiong, Ramon C. Sun, Matthew S. Gentry, Hiromi Sesaki, Tianyan Gao

Markey Cancer Center Faculty Publications

Metabolic reprogramming has been recognized as one of the major mechanisms that fuel tumor initiation and progression. Our previous studies demonstrate that activation of Drp1 promotes fatty acid oxidation and downstream Wnt signaling. Here we investigate the role of Drp1 in regulating glycogen metabolism in colon cancer. Knockdown of Drp1 decreases mitochondrial respiration without increasing glycolysis. Analysis of cellular metabolites reveals that the levels of glucose-6-phosphate, a precursor for glycogenesis, are significantly elevated whereas pyruvate and other TCA cycle metabolites remain unchanged in Drp1 knockdown cells. Additionally, silencing Drp1 activates AMPK to stimulate the expression glycogen synthase 1 (GYS1) mRNA …

Phosphatidic Acid Binding To Patched Contributes To The Inhibition Of Smoothened And Hedgehog Signaling In Drosophila Wing Development, Jie Zhang, Yajuan Liu, Chi Wang, Craig W. Vander Kooi, Jianhang Jia

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling controls growth and patterning during embryonic development and homeostasis in adult tissues. Hh binding to the receptor Patched (Ptc) elicits intracellular signaling by relieving Ptc-mediated inhibition of the transmembrane protein Smoothened (Smo). We uncovered a role for the lipid phosphatidic acid (PA) in the regulation of the Hh pathway in Drosophila melanogaster. Deleting the Ptc C-terminal tail or mutating the predicted PA-binding sites within it prevented Ptc from inhibiting Smo in wing discs and in cultured cells. The C-terminal tail of Ptc directly interacted with PA in vitro, an association that was reduced by Hh, and increased …

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …

Regulated Translocation Of Neutral Sphingomyelinase-2 To The Plasma Membrane Drives Insulin Resistance In Steatotic Hepatocytes, Salim S. El-Amouri, Alexander A. Karakashian, Erhard Bieberich, Mariana N. Nikolova‑Karakashian

Markey Cancer Center Faculty Publications

Abstract Obesity-associated diabetes is linked to the accumulation of ceramide in various organs, including the liver. The exact mechanisms by which ceramide contributes to diabetic pathology are unclear, but one proposed scenario is that ceramide accumulation may inhibit insulin signaling pathways. It is unknown however whether the excess ceramide is generated proximal to the insulin receptor, that is, at the plasma membrane (PM), where it could affect the insulin signaling pathway directly, or the onset of insulin resistance is due to ceramide- induced mitochondrial dysfunction and/or lipotoxicity. Using hepatic cell lines and primary cultures, gain- and loss- of function approach, …

Rit1 Regulation Of Cns Lipids Rit1 Deficiency Alters Cerebral Lipid Metabolism And Reduces White Matter Tract Oligodendrocytes And Conduction Velocities, Lei Wu, Fang Wang, Carole L. Moncman, Mritunjay Pandey, Harrison A. Clarke, Hilaree N. Frazier, Lyndsay E. A. Young, Matthew S. Gentry, Weikang Cai, Olivier Thibault, Ramon C. Sun, Douglas A. Andres

Markey Cancer Center Faculty Publications

Oligodendrocytes (OLs) generate lipid-rich myelin membranes that wrap axons to enable efficient transmission of electrical impulses. Using a RIT1 knockout mouse model and in situ high- resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) coupled with MS-based lipidomic analysis to determine the contribution of RIT1 to lipid homeostasis. Here, we report that RIT1 loss is associated with altered lipid levels in the central nervous system (CNS), including myelin-associated lipids within the corpus callosum (CC). Perturbed lipid metabolism was correlated with reduced numbers of OLs, but increased numbers of GFAP+ glia, in the CC, but not in grey matter. This was …

Stat3 Modulates Cd4+ T Mitochondrial Dynamics And Function In Aging, Emelia Zukowski, Marco Sannella, Jack Donato Rockhold, Gabriella Kalantar, Jingting Yu, Sara Santacruz-Calvo, Madison K. Kuhn, Nasun Hah, Ling Ouyang, Tzu-Wen Wang, Lyanne Murphy, Heather Marszalkowski, Kaleigh Gibney, Micah J. Drummond, Elizabeth A. Proctor, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Markey Cancer Center Faculty Publications

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and …

The Stop Program: A Hybrid Smoking Prevention And Cessation Training For Cancer Care Providers In Colombia And Peru, Irene Tamí-Maury, Samuel Tundealao, Vilma Díaz, Elizabeth Ochoa, Esperanza Garcia, Johanna Rincon, Valeri Noé-Díaz, Carlos Castañeda, Jesús Acosta, María Fernández, Tatiana Vidaurre, John Crowley

Faculty, Staff and Student Publications

We designed and tested the feasibility of the Smoking Cessation Training Program for Oncology Practice (STOP), a hybrid (face-to-face plus web-based) educational intervention to enhance Spanish-speaking cancer care professionals' (CCPs') ability to provide brief smoking prevention and cessation counseling to cancer patients and survivors. Changes in the CCPs' competencies (knowledge, attitude, self-efficacy, and practices toward smoking and smoking cessation services) were assessed post-training. Sixty CCPs from one major cancer center in Colombia (n = 30) and Peru (n = 30) were invited to participate in a 4-module hybrid training program on smoking prevention and cessation. Demographic and pre- and post-test …

Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Controversy And Consensus On The Management Of Elevated Sperm Dna Fragmentation In Male Infertility: A Global Survey, Current Guidelines, And Expert Recommendations, Ala'a Farkouh, Ashok Agarwal, Taha Abo-Almagd Abdel-Meguid Hamoda, Parviz Kavoussi, Ramadan Saleh, Armand Zini, Mohamed Arafa, Ahmed M Harraz, Murat Gul, Vilvapathy Senguttuvan Karthikeyan, Damayanthi Durairajanayagam, Amarnath Rambhatla, Florence Boitrelle, Eric Chung, Ponco Birowo, Tuncay Toprak, Ramy Abou Ghayda, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Fotios Dimitriadis, Giorgio I Russo, Ioannis Sokolakis, Taymour Mostafa, Konstantinos Makarounis, Imad Ziouziou, Shinnosuke Kuroda, Marion Bendayan, Raneen Sawaid Kaiyal, Andrian Japari, Mara Simopoulou, Lucia Rocco, Nicolas Garrido, Nazim Gherabi, Kadir Bocu, Oguzhan Kahraman, Tan V Le, Christine Wyns, Kelton Tremellen, Selcuk Sarikaya, Sheena Lewis, Donald P Evenson, Edmund Ko, Aldo E Calogero, Fahmi Bahar, Marlon Martinez, Andrea Crafa, Quang Nguyen, Rafael F Ambar, Giovanni Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alarbid, Akira Tsujimura, Alireza Kheradmand, Christina Anagnostopoulou, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Germar-Michael Pinggera, Priyank Kothari, Nasser Mogharabian, Sava Micic, Sheryl Homa, Sara Darbandi, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Marjan Sabbaghian, Wael Ibrahim, Ryan P Smith, Christopher Chee Kong Ho, Jean De La Rosette, Ahmed I El-Sakka, Mirko Preto, Cătălina Zenoaga-Barbăroșie, Saad Mohammed Abumelha, Aykut Baser, Kaan Aydos, Liliana Ramirez-Dominguez, Vijay Kumar, Teng Aik Ong, Tiago Cesar Mierzwa, Ricky Adriansjah, Saleem A Banihani, Kasonde Bowa, Shinichiro Fukuhara, Marcelo Rodriguez Peña, Mohamad Moussa, Umut Çağın Ari, Chak-Lam Cho, Nicholas N Tadros, Muhammet Rasit Ugur, Edouard Amar, Marco Falcone, Frederic Romain Santer, Arif Kalkanli, Keshab Kumar Karna, Kareim Khalafalla, Ranjit B Vishwakarma, Federica Finocchi, Carlo Giulioni, Erman Ceyhan, Gökhan Çeker, Chadi Yazbeck, Osvaldo Rajmil, Mehmet Yilmaz, Baris Altay, Trenton L Barrett, Kay Seong Ngoo, Shubhadeep Roychoudhury, Gianmaria Salvio, Haocheng Lin, Ates Kadioglu, Massimiliano Timpano, Tomer Avidor-Reiss, Lukman Hakim, Puneet Sindhwani, Giorgio Franco, Rajender Singh, Filippo Giacone, Mikhail Ruzaev, Raghavender Kosgi, Nikolaos Sofikitis, Ayad Palani, Gokhan Calik, Deniz Kulaksız, Davor Jezek, Manaf Al Hashmi, Panagiotis Drakopoulos, Huda Omran, Sofia Leonardi, Ciler Celik-Ozenci, Nur Dokuzeylül Güngör, Jonathan Ramsay, Toshiyasu Amano, Emrullah Sogutdelen, Gede Wirya Kusuma Duarsa, Koji Chiba, Sunil Jindal, Missy Savira, Luca Boeri, Edson Borges, Deepak Gupte, Fatih Gokalp, Guadalupe Hernández Hebrard, Suks Minhas, Rupin Shah, Global Andrology Forum

Faculty, Staff and Student Publications

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition.

Materials and methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate …