Medical Specialties Commons^™

Lac-Phe Mediates The Effects Of Metformin On Food Intake And Body Weight, Shuke Xiao, Veronica L Li, Xuchao Lyu, Xudong Chen, Wei Wei, Fahim Abbasi, Joshua W Knowles, Alan Sheng-Hwa Tung, Shuliang Deng, Gaurav Tiwari, Xu Shi, Shuning Zheng, Laurie Farrell, Zsu-Zsu Chen, Kent D Taylor, Xiuqing Guo, Mark O Goodarzi, Alexis C Wood, Yii-Der Ida Chen, Leslie A Lange, Stephen S Rich, Jerome I Rotter, Clary B Clish, Usman A Tahir, Robert E Gerszten, Mark D Benson, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin’s effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the …

European Society Of Coloproctology Guideline On Training In Robotic Colorectal Surgery (2024), Samson Tou, Stephanie Au, Cillian Clancy, Steven Clarke, Danielle Collins, Frances Dixon, Elizabeth Dreher, Christina Fleming, Anthony G Gallagher, Marcos Gomez-Ruiz, Jos Kleijnen, Yasuko Maeda, Katie Rollins, Klaus E Matzel

Staff and Researcher Publications

No abstract provided.

Tachycardia And Atrial Fibrillation-Related Cardiomyopathies: Potential Mechanisms And Current Therapies, Joshua A Keefe, Rebecca Garber, Mark D Mccauley, Xander H T Wehrens

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is associated with an increased risk of new-onset ventricular contractile dysfunction, termed arrhythmia-induced cardiomyopathy (AIC). Although cardioembolic stroke remains the most feared and widely studied complication of AF, AIC is also a clinically important consequence of AF that portends significant morbidity and mortality to patients with AF. Current treatments are aimed at restoring sinus rhythm through catheter ablation and rate and rhythm control, but these treatments do not target the underlying molecular mechanisms driving the progression from AF to AIC. Here, we describe the clinical features of the various AIC subtypes, discuss the pathophysiologic mechanisms driving the …

Hepatocellular Carcinoma Screening In A Contemporary Cohort Of At-Risk Patients, Darine Daher, Karim Seif El Dahan, Nicole E Rich, Nabihah Tayob, Vincent Merrill, Daniel Q Huang, Ju Dong Yang, Anand V Kulkarni, Fasiha Kanwal, Jorge Marrero, Neehar Parikh, Amit G Singal

Faculty, Staff and Students Publications

IMPORTANCE: Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases.

OBJECTIVE: To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 …

The Satb1-Mir22-Gba Axis Mediates Glucocerebroside Accumulation Inducing A Cellular Senescence-Like Phenotype In Dopaminergic Neurons, Taylor Russo, Benjamin Kolisnyk, Aswathy B S, Jonathan Plessis-Belair, Tae Wan Kim, Jacqueline Martin, Jason Ni, Jordan A Pearson, Emily J Park, Roger B Sher, Lorenz Studer, Markus Riessland

Faculty, Staff and Students Publications

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype …

An Evidence-Based Update On Anticholinergic Use For Drug-Induced Movement Disorders, Nora Vanegas-Arroyave, Stanley N Caroff, Leslie Citrome, Jovita Crasta, Roger S Mcintyre, Jonathan M Meyer, Amita Patel, J Michael Smith, Khody Farahmand, Rachel Manahan, Leslie Lundt, Samantha A Cicero

Faculty, Staff and Students Publications

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception …

Severity-Adjusted Evaluation Of Liver Transplantation On Health Outcomes In Urea Cycle Disorders, Roland Posset, Sven F Garbade, Florian Gleich, Svenja Scharre, Jürgen G Okun, Andrea L Gropman, Sandesh C S Nagamani, Ann-Catrin Druck, Friederike Epp, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Purpose: Liver transplantation (LTx) is performed in individuals with urea cycle disorders when medical management (MM) insufficiently prevents the occurrence of hyperammonemic events. However, there is a paucity of systematic analyses on the effects of LTx on health-related outcome parameters compared to individuals with comparable severity who are medically managed.

Methods: We investigated the effects of LTx and MM on validated health-related outcome parameters, including the metabolic disease course, linear growth, and neurocognitive outcomes. Individuals were stratified into "severe" and "attenuated" categories based on the genotype-specific and validated in vitro enzyme activity.

Results: LTx enabled metabolic stability by prevention of …

The Role Of Epigenetic Mechanisms In The Long-Term Effects Of Early-Life Adversity And Mother-Infant Relationship On Physiology And Behavior Of Offspring In Laboratory Rats And Mice, Olga V Burenkova, Elena L Grigorenko

Faculty, Staff and Students Publications

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of …

Prescription And Dispensation Of Qt-Prolonging Medications In Individuals Receiving Hemodialysis, Virginia Wang, Chin-Hua Lily Wang, Magdalene M Assimon, Patrick H Pun, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

IMPORTANCE: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population.

OBJECTIVE: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis.

DESIGN, …

Alveolar Epithelial Cell Dysfunction In Idiopathic Pulmonary Fibrosis Linked To Lipid Alterations: Therapeutic Implications, Francesca Polverino, Ana Mora

Faculty, Staff and Students Publications

No abstract provided.

A Mutation In Tbxt Causes Congenital Vertebral Malformations In Humans And Mice, Shuxia Chen, Yunping Lei, Yajun Yang, Chennan Liu, Lele Kuang, Li Jin, Richard H Finnell, Xueyan Yang, Hongyan Wang

Faculty, Staff and Students Publications

T-box transcription factor T (TBXT; T) is required for mesodermal formation and axial skeletal development. Although it has been extensively studied in various model organisms, human congenital vertebral malformations (CVMs) involving T are not well established. Here, we report a family with 15 CVM patients distributed across 4 generations. All affected individuals carry a heterozygous mutation, T c.596A>G (p.Q199R), which is not found in unaffected family members, indicating co-segregation of the genotype and phenotype. In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity, but reduces its transcriptional activity compared to the wild-type. …

Immunologic Basis For Development Of Keratoconjunctivitis Sicca In Systemic Autoimmune Diseases: Role Of Innate Immune Sensors, Michael E Stern, Argyrios N Theofilopoulos, Philipp Steven, Jerry Y Niederkorn, Robert Fox, Margarita Calonge, Christof Scheid, Stephen C Pflugfelder

Faculty, Staff and Students Publications

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign …

Temporary Peripheral Nerve Stimulation For The Treatment Of Greater Occipital Neuralgia, Royce Copeland, Angela Nwankwo, Emanuel Narcis Husu

Faculty, Staff and Students Publications

Background: Greater occipital neuralgia (GON), a cause of chronic headaches, can be debilitating and vastly affect one's quality of life. Recent strides in comprehending the pathophysiology of GON and the ongoing evolution of approaches to the condition's treatment have led to the pursuit of more effective interventions. Among these, temporary peripheral nerve stimulation (PNS) devices have surfaced as an avenue for management, presenting a minimally invasive yet highly efficient alternative in treating other chronic pain conditions. This study discusses a case of GON successfully managed with temporary (60-day) PNS.

Case report: A 35-year-old man presented with a nearly 8-month history …

Tgf-Β1 And Tgf-Βr1 Variants Are Associated With Clinical Outcomes In Smoking-Related Head And Neck Cancer Patients Treated With Chemoradiation Through Modulating Microrna-Mediated Regulation, Zihao Niu, Peng Sun, Mark E Zafereo, Hongliang Liu, Peng Wei, Jia Wu, Neil D Gross, Sanjay Shete, Qingyi Wei, Guibin Zheng, Andy G Sikora, George A Calin, Guojun Li

Faculty, Staff and Student Publications

TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or …

Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer

Department of Radiation Oncology Faculty Papers

Background

Adaptive radiation therapy (ART) offers a dynamic approach to address structural and spatial changes that occur during radiotherapy (RT) for locally advanced head and neck cancers. The integration of daily ART with Cone-Beam CT (CBCT) imaging presents a solution to enhance the therapeutic ratio by addressing inter-fractional changes.

Methods

We evaluated the initial clinical experience of daily ART for patients with head and neck cancer using an online adaptive platform with intelligence-assisted workflows on daily CBCT. Treatment included auto-contour and structure deformation of Organs at Risk (OARs) and target structures, with adjustments by the treating physician. Two plans were …

Randomized Controlled Trial Of The Cmr Immersive Virtual Reality (Ivr) Headset Training Compared To E-Learning For Operating Room Configuration Of The Cmr Versius Robot, Catherine L Eley, Varun Palaniappan, Abbie Carter, Opeyemi Sogaolu, James Horwood, Michael Davies, Jared Torkington, James Ansell

Faculty, Staff and Student Publications

Robotic surgery offers potential advantages over laparoscopic procedures, but the training for configuring robotic systems in the operating room remains underexplored. This study seeks to validate immersive virtual reality (IVR) headset training for setting up the CMR Versius in the operating room. This single-blinded randomized control trial randomised medical students with no prior robotic experience using an online randomiser. The intervention group received IVR headset training, and the control group, e-learning modules. Assessors were blinded to participant group. Primary endpoint was overall score (OS): Likert-scale 1-5: 1 reflecting independent performance, with increasing verbal prompts to a maximum score of 5, …

The Psychological Burden Of Nmosd - A Mixed Method Study Of Patients And Caregivers, Darcy C. Esiason, Nicole Ciesinski, Chelsi N. Nurse, Wendy Erler, Tom Hattrich, Ankita Deshpande, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system with common symptoms of rapid onset of eye pain, loss of vision, neck/back pain, paralysis, bowel and bladder dysfunction and heat sensitivity. The rare, unpredictable, and debilitating nature of NMOSD constitutes a unique psychological burden for patients and their caregivers, the specific nature and extent of which is not yet known. This mixed methods study, informed by both quantitative and qualitative data collected via self-report measures, focus groups, and in-depth interviews, aims to investigate and understand the psychological burden of patients with NMOSD and their caregiver/loved …

Activation Of Endogenous Retroviruses And Induction Of Viral Mimicry By Mek1/2 Inhibition In Pancreatic Cancer, Alice Cortesi, Francesco Gandolfi, Fabiana Arco, Pierluigi Di Chiaro, Emanuele Valli, Sara Polletti, Roberta Noberini, Francesco Gualdrini, Sergio Attanasio, Francesca Citron, I-Lin Ho, Rutvi Shah, Er-Yen Yen, Mara Cetty Spinella, Simona Ronzoni, Simona Rodighiero, Nico Mitro, Tiziana Bonaldi, Serena Ghisletti, Silvia Monticelli, Andrea Viale, Giuseppe Riccardo Diaferia, Gioacchino Natoli

Faculty, Staff and Student Publications

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes. We tracked ERV activation …

Non-Thermal Plasma Reduces Hsv-1 Infection Of And Replication In Hacat Keratinocytes In Vitro, Julia Sutter, Jascha Brettschneider, Brian Wigdahl, Peter Bruggeman, Fred Krebs, Vandana Miller

Kimmel Cancer Center Faculty Papers

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP …

Visual Analysis Of Bone Malignancies Immunotherapy: A Bibliometric Analysis From 2010 To 2023, Kaiyu Shen, Liu Yang, Shuaiyi Ke, Wencang Gao

Faculty, Staff and Student Publications

Background: Bone malignancies (BM), including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and chordoma, are characterized by high rates of recurrence and mortality, despite the availability of diverse treatment approaches. Immunotherapy has gained increasing importance in cancer treatment. However, there is a lack of comprehensive studies that utilize bibliometric analysis to explore immunotherapy for BM.

Methods: A literature search of English studies on BM and immunotherapy from 2010 to 2023 was conducted in the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were utilized to examine global trends and research hotspots in this field.

Results: …

Pre-Covid-19 Hospital Quality And Hospital Response To Covid-19: Examining Associations Between Risk-Adjusted Mortality For Patients Hospitalised With Covid-19 And Pre-Covid-19 Hospital Quality, Doris Peter, Shu-Xia Li, Yongfei Wang, Jing Zhang, Jacqueline Grady, Kerry Mcdowell, Erica Norton, Zhenqiu Lin, Susannah Bernheim, Arjun K Venkatesh, Lee A Fleisher, Michelle Schreiber, Lisa G Suter, Elizabeth W Triche

Faculty, Staff and Student Publications

OBJECTIVES: The extent to which care quality influenced outcomes for patients hospitalised with COVID-19 is unknown. Our objective was to determine if prepandemic hospital quality is associated with mortality among Medicare patients hospitalised with COVID-19.

DESIGN: This is a retrospective observational study. We calculated hospital-level risk-standardised in-hospital and 30-day mortality rates (risk-standardised mortality rates, RSMRs) for patients hospitalised with COVID-19, and correlation coefficients between RSMRs and pre-COVID-19 hospital quality, overall and stratified by hospital characteristics.

SETTING: Short-term acute care hospitals and critical access hospitals in the USA.

PARTICIPANTS: Hospitalised Medicare beneficiaries (Fee-For-Service and Medicare Advantage) age 65 and older hospitalised …

Regional Analysis To Delineate Intrasample Heterogeneity With Regionalst, Yue Lyu, Chong Wu, Wei Sun, Ziyi Li

Faculty, Staff and Student Publications

MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human diseases. Intra-tumor heterogeneity, e.g. may be associated with cancer treatment responses. However, the lack of computational tools for exploiting cross-regional information and the limited spatial resolution of current technologies present major obstacles to elucidating tissue heterogeneity.

RESULTS: To address these challenges, we introduce RegionalST, an efficient computational method that enables users to quantify cell type mixture and interactions, identify sub-regions of interest, and perform cross-region cell type-specific differential analysis for the first time. Our simulations …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissuejove: Peer Reviewed Scientific Video Journal Article Protocols, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Faculty, Staff and Students Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Gut Microbiota And Blood Metabolites Related To Fiber Intake And Type 2 Diabetes, Zheng Wang, Brandilyn A Peters, Bing Yu, Megan L Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R Isasi, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).

METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissue, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Challenges And Considerations Of Preclinical Development For Ipsc-Based Myogenic Cell Therapy, Congshan Sun, Carlo Serra, Brianna Harley Kalicharan, Jeffrey Harding, Mahendra Rao

Faculty, Staff and Students Publications

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells …

Cancer Biomarkers: Emerging Trends And Clinical Implications For Personalized Treatment, Antonio Passaro, Maise Al Bakir, Emily G Hamilton, Maximilian Diehn, Fabrice André, Sinchita Roy-Chowdhuri, Giannis Mountzios, Ignacio I Wistuba, Charles Swanton, Solange Peters

Faculty, Staff and Student Publications

The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, …

Gpr56 In Gvl: Marker Or Mechanism?, Audra N Iness, Pavan Bachireddy

Faculty, Staff and Student Publications

No abstract provided.

Embracing Cancer Complexity: Hallmarks Of Systemic Disease, Charles Swanton, Elsa Bernard, Chris Abbosh, Fabrice André, Johan Auwerx, Allan Balmain, Dafna Bar-Sagi, René Bernards, Susan Bullman, James Degregori, Catherine Elliott, Ayelet Erez, Gerard Evan, Mark A Febbraio, Andrés Hidalgo, Mariam Jamal-Hanjani, Johanna A Joyce, Matthew Kaiser, Katja Lamia, Jason W Locasale, Sherene Loi, Ilaria Malanchi, Miriam Merad, Kathryn Musgrave, Ketan J Patel, Sergio Quezada, Jennifer A Wargo, Ashani Weeraratna, Eileen White, Frank Winkler, John N Wood, Karen H Vousden, Douglas Hanahan

Faculty, Staff and Student Publications

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism …

The Remission Status Of Aml Patients After Allo-Hct Is Associated With A Distinct Single-Cell Bone Marrow T-Cell Signature, Anna Mathioudaki, Xizhe Wang, David Sedloev, Richard Huth, Aryan Kamal, Michael Hundemer, Yi Liu, Spyridoula Vasileiou, Premal Lulla, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tim Sauer, Michael Schmitt, Judith B Zaugg, Caroline Pabst

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in …