Medical Specialties Commons^™

Case Report: Durable Remission After Abscopal Effect Following Transcatheter Hepatic Arterial Embolization In A Patient With Mucosal Melanoma Refractory To Immunotherapy, Lynsey M Claus, Hannah E Kostan, Marshall E Hicks, Rony Avritscher, Michael A Davies

Faculty, Staff and Student Publications

Mucosal melanoma, a rare subtype of melanoma affecting mucosal surfaces, presents significant challenges in diagnosis and treatment, particularly due to its low programmed death-ligand 1 (PD-L1) expression and reduced response to immune checkpoint inhibitors (ICIs). This case report describes a 58-year-old woman with metastatic nasal mucosal melanoma initially resistant to neoadjuvant ipilimumab and nivolumab. After undergoing hepatic transcatheter arterial embolization, she experienced an unexpected abscopal effect, where distant metastases showed near-complete resolution despite prior lack of response to immunotherapy. The patient's disease initially progressed despite two cycles of ICI treatment, and further immunotherapy with nivolumab and relatimab did not improve …

Editorial: Molecular Mechanisms And Targeted Therapies For Colorectal Cancer Vol Ii, Alessandro Passardi, David Gibbons, Antonio Mario Scanu, Shilpa S Dhar

Faculty, Staff and Student Publications

No abstract provided.

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Molecular Alterations In Idh-Mutant Astrocytoma: A Multi-Institutional Retrospective Study, Keng Lam, Hanim I Ozkizilkaya, Denái R Milton, Antonio Dono, Yajie Liu, Suprateek Kundu, Vinodh A Kumar, Jason M Johnson, Yoshua Esquenazi, Chirag B Patel, Leomar Y Ballester

Faculty, Staff and Student Publications

Background: Several molecular alterations have been identified to provide prognosis for patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary baseline survival data with respect to their molecular alterations are lacking. The prognostic value of histologic grading remains controversial.

Methods: This was a retrospective multi-site study of adult IDH-mutant diffuse astrocytoma patients. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations between OS and measures of interest were evaluated using Cox proportional hazards regression models.

Results: We identified 241 eligible patients. The most frequent mutations were IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), …

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

Ganglioside Gd2 Contributes To A Stem-Like Phenotype In Intrahepatic Cholangiocarcinoma, Antonella Mannini, Mirella Pastore, Alessia Giachi, Margherita Correnti, Elena Spínola Lasso, Tiziano Lottini, Benedetta Piombanti, Ignazia Tusa, Elisabetta Rovida, Cédric Coulouarn, Jesper B Andersen, Monika Lewinska, Claudia Campani, V Lokesh Battula, Bin Yuan, Massimo Aureli, Emma V Carsana, Caterina Peraldo Neia, Paola Ostano, Alessia Tani, Daniele Nosi, Anna Vanni, Laura Maggi, Luca Di Tommaso, Giuseppina Comito, Stefania Madiai, Annarosa Arcangeli, Fabio Marra, Chiara Raggi

Faculty, Staff and Student Publications

BACKGROUND & AIMS: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

METHODS: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT-qPCR. The …

Ft538, Ipsc-Derived Nk Cells, Enhance Aml Cell Killing When Combined With Chemotherapy, Amanda Eckstrom, Anudishi Tyagi, Sajid Mahmood, Lilly Wong, Bahram Valamehr, Adishwar Rao, Akriti Agrawal, Maryam Siddiqui, V Lokesh Battula

Faculty, Staff and Student Publications

Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines …

18 Kda Translocator Protein (Tspo) Is Upregulated In Rat Brain After Peripheral Nerve Injury And Downregulated By Diroximel Fumarate, Rafael A Cazuza, Sever M Zagrai, Anamaria R Grieco, Thomas D Avery, Andrew D Abell, Hsiao-Ying Wey, Marco L Loggia, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments. We used positron emission tomography-computed tomography (PET-CT) and [18F]-PBR06 radioligand to measure TSPO levels in the brain across time after chronic constriction injury (CCI) of the sciatic nerve in both male and female rats. Up to 10 weeks post-CCI, TSPO expression was …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Approach To Determining Etiology Of Hypophosphatemia In A Patient With Coexisting Phosphaturic Mesenchymal Tumor And Fibrous Dysplasia, Madhuri D Patil, Sintawat Wangsiricharoen, Alexander J Lazar, Bryan Moon, John E Madewell, Michael T Collins, Theresa A Guise

Faculty, Staff and Student Publications

Dysregulated FGF23 production is a demonstrated cause of hypophosphatemia and osteomalacia. Diseases associated with these conditions include phosphaturic mesenchymal tumor (PMT) causing tumor induced osteomalacia, various forms of rickets, and fibrous dysplasia (FD). Coexistence of 2 conditions that can increase FGF23 concentrations is rare. We report a case of a 79-yr-old man who presented with rib and right flank pain. Imaging revealed bone lesions in the right iliac wing, left supra-acetabular area, and L4 vertebral body. Biopsies showed a right iliac PMT and left supra-acetabular FD. Cryoablation of both lesions resolved the phosphaturia with normalization of phosphorus level. Coexistence of …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Optimal Timing Of Organs-At-Risk-Sparing Adaptive Radiation Therapy For Head-And-Neck Cancer Under Re-Planning Resource Constraints, Fatemeh Nosrat, Cem Dede, Lucas B Mccullum, Raul Garcia, Abdallah S R Mohamed, Jacob G Scott, James E Bates, Brigid A Mcdonald, Kareem A Wahid, Mohamed A Naser, Renjie He, Aysenur Karagoz, Amy C Moreno, Lisanne V Van Dijk, Kristy K Brock, Jolien Heukelom, Seyedmohammadhossein Hosseinian, Mehdi Hemmati, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

Background and purpose: Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-planning, which represent one-size-fits-all approaches and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing of re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, for patients with head and neck cancer (HNC).

Materials and methods: A novel Markov decision process (MDP) model was developed to determine optimal timing of re-planning based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for …

Micrornas As Key Regulators Of Cancer Drug Resistance: Insights And Future Directions In Chemotherapy, Targeted-Therapy, Radiotherapy, And Immunotherapy, Michael Attathikhun, Ancuta Jurj, George A Calin

Faculty, Staff and Student Publications

Cancer therapy remains an active field of investigation, particularly in understanding and overcoming therapy resistance. Small non-coding RNAs, such as microRNAs (miRNAs), are emerging as key regulators of cancer survival, progression, proliferation, invasion, migration, and metastasis. Although many studies have linked miRNAs to cancer therapy outcomes, significant questions remain regarding their precise molecular and cellular roles in therapy resistance. Increasing evidence shows that miRNAs influence critical pathways such as apoptosis, immune evasion, and other signaling cascades. However, there have been many setbacks because of the limitations in knowledge of each specific miRNA's function. A deeper understanding of miRNA expression and …

Corrigendum To Exosomal Mirna Confers Chemo Resistance Via Targeting Cav1/P-Gp/M2-Type Macrophage Axis In Ovarian Cancer, Pinar Kanlikilicer, Recep Bayraktar, Merve Denizli, Mohammed H Rashed, Cristina Ivan, Burcu Aslan, Rahul Mitra, Kubra Karagoz, Emine Bayraktar, Xinna Zhang, Cristian Rodriguez-Aguayo, Amr Ahmed El-Arabey, Nermin Kahraman, Seyda Baydogan, Ozgur Ozkayar, Michael L Gatza, Bulent Ozpolat, George A Calin, Anil K Sood, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

No abstract provided.

Fraud In Genetic Testing: Swindling The System, Rachel Notestine, Claire N Singletary, Meagan Choates, Stephanie Gandomi, Molly Daniels, Rebecca Lunstroth, Quinn Stein

Faculty, Staff and Student Publications

Purpose: Health care fraud comprises a sizable portion of United States health care expenditure and inflicts undue burden on payors, patients, and the health care system overall. The genetic testing industry is rapidly growing, which propagates opportunities for health care fraud. Although federal organizations have highlighted it as an issue, there is limited research exploring genetic testing fraud.

Methods: A retrospective review of federal websites, news articles, and a legal database resulted in 42 cases of fraud involving outpatient genetic testing published between February 2019 and December 2023. These cases were analyzed for themes via inductive conventional content analysis.

Results: …

Burden Of Seasonal Human Coronavirus Infections In Hematopoietic Cell Transplant Recipients, Fareed Khawaja, Terri Lynn Shigle, Layale Yaghi, May Daher, Jeremy L Ramdial, Ella Ariza-Heredia, Ying Jiang, Roy F Chemaly

Faculty, Staff and Student Publications

Background: Community respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.

Methods: We performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respiratory viral infections in HCT recipients. Patient data were collected to identify risk factors for HCoV LRI, and to calculate …

Mechanical Regulation Of Macrophage Metabolism By Allograft Inflammatory Factor 1 Leads To Adverse Remodeling After Cardiac Injury, Matthew Deberge, Kristofor Glinton, Connor Lantz, Zhi-Dong Ge, David P Sullivan, Swapna Patil, Bo Ryung Lee, Minori I Thorp, Adam Mullick, Steve Yeh, Shuling Han, Anja M Van Der Laan, Hans W M Niessen, Xunrong Luo, Nicholas E S Sibinga, Edward B Thorp

Faculty, Staff and Student Publications

Myocardial infarction (MI) mobilizes macrophages, the central protagonists of tissue repair in the infarcted heart. Although necessary for repair, macrophages also contribute to adverse remodeling and progression to heart failure. In this context, specific targeting of inflammatory macrophage activation may attenuate maladaptive responses and enhance cardiac repair. Allograft inflammatory factor 1 (AIF1) is a macrophage-specific protein expressed in a variety of inflammatory settings, but its function after MI is unknown. Here we identify a maladaptive role for macrophage AIF1 after MI in mice. Mechanistic studies show that AIF1 increases actin remodeling in macrophages to promote reactive oxygen species-dependent activation of …

Erratum: Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification: Erratum, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

No abstract provided.

Continued Positive Job Search Experience For New Pathologists Seeking First Employment During The Covid-19 Pandemic (2020-2022), Julie Katz Karp, Amanda Lofgreen, Kristen Johnson, Melissa R George, Stephanie Barak, Bronwyn H Bryant, Mary P Berg, John M Childs, Barbara E C Knollman-Ritschel, Victor G Prieto, Kristie L White, Cindy B Mccloskey

Faculty, Staff and Student Publications

Context.—: As pathologists retire and leave the field, it is critical to accurately capture employment trends for new-in-practice pathologists. There is always interest in the job market for newly graduated pathology trainees and prospective pathology trainees, but it is unclear how the COVID-19 pandemic may have affected the job search experience.

Objective.—: To provide an update on trends gleaned from a survey of pathology graduates' job search experiences during the COVID-19 pandemic.

Design.—: We analyzed data from an annual job search survey sent by the College of American Pathologists Graduate Medical Education Committee between 2020 and 2022 to College of …

Effectiveness And Acceptability Of Ventilation Modifications In Healthcare Facilities, Liberia 2022–2023, Ronan F Arthur, Ashley Styczynski, Krithika Srinivasan, Amos Tandanpolie, Philip Bemah, Ethan Bell, Jason R Andrews, Tom Baer, Jorge L Salinas

Faculty, Staff and Student Publications

Objective: To evaluate the effectiveness and acceptability of ventilation interventions in naturally ventilated hospitals in Liberia.

Design: Difference-in-differences analysis of pre- and post-air changes per hour of intervention and control spaces.

Setting: Hospitals in Bong and Montserrado Counties, Liberia.

Participants: Seventy patient care spaces were evaluated at baseline. Six spaces underwent physical intervention modifications, while 2 spaces were assessed for indirect effects and 2 others used as controls. Healthcare workers were interviewed to assess ventilation knowledge and acceptability.

Interventions: Ventilation interventions included the installation of window screens, louvered doors and windows, and wind turbines.

Methods: We measured carbon dioxide levels …

Partial Agonism In Heteromeric Gluk2/Gluk5 Kainate Receptor, Nabina Paudyal, Anindita Das, Elisa Carrillo, Vladimir Berka, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Kainate receptors are a subtype of ionotropic glutamate receptors that form transmembrane channels upon binding glutamate. Here, we have investigated the mechanism of partial agonism in heteromeric GluK2/K5 receptors, where the GluK2 and GluK5 subunits have distinct agonist binding profiles. Using single-molecule Förster resonance energy transfer, we found that at the bi-lobed agonist-binding domain, the partial agonist AMPA-bound receptor occupied intermediate cleft closure conformational states at the GluK2 cleft, compared to the more open cleft conformations in apo form and more closed cleft conformations in the full agonist glutamate-bound form. In contrast, there is no significant difference in cleft closure …

Tnik-Driven Regulation Of Erk5 Transcriptional Activity In Endothelial Cells, Venkata Subrahmanya Kumar Samanthapudi, Sivareddy Kotla, Nhat-Tu Le

Faculty, Staff and Student Publications

Extracellular signal-regulated kinase 5 (ERK5) is essential for cardiovascular development and endothelial cell (EC) function. Activation of ERK5 through MEK5-mediated phosphorylation at threonine 218 and tyrosine 220 (T218/Y220) drives the transcriptional activation of myocyte enhancer factor-2 (MEF2), promoting the expression of KLF2 and KLF4—key transcription factors that maintain vascular homeostasis. We previously demonstrated that ponatinib suppresses ERK5 transcriptional activity without affecting laminar-flow (l-flow)-induced T218/Y220 phosphorylation, suggesting a non-canonical regulatory mechanism. Since ponatinib inhibits Traf2- and Nck-interacting kinase (TNIK), we hypothesized that TNIK modulates ERK5 transcriptional activity. Using a mammalian one-hybrid assay and quantitative RT-PCR (qRT-PCR), we show that TNIK …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

Correspondence To Editorial 2 On "Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial", Sun Young Yim, Sung Hwan Lee, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Dosimetric Evaluations Using Cycle-Consistent Generative Adversarial Network Synthetic Ct For Mr-Guided Adaptive Radiation Therapy, Gabriel L Asher, Shiru Wang, Bassem I Zaki, Gregory A Russo, Gobind S Gill, Charles R Thomas, Temiloluwa O Prioleau, Yuting Li, Rongxiao Zhang, Yue Yan, Brady Hunt

Faculty, Staff and Student Publications

Background: Magnetic resonance (MR) guided radiation therapy combines high-resolution image capabilities of MRI with the precise targeting of radiation therapy. However, MRI does not provide the essential electron density information for accurate dose calculation, which limit the application of MRI. In this presented work, we evaluated the potential for Deep Learning (DL) based synthetic CT (sCT) generation using 3D MRI setup scans acquired during real-time adaptive MRI-guided radiation therapy.

Methods: We trained and evaluated a Cycle-consistent Generative Adversarial Network (Cycle-GAN) using paired MRI and deformably registered CT scan slices (dCT) in the context of real-time adaptive MRI-guided radiation therapy. Synthetic …

A Phase Ib/Ii Trial Of Neoadjuvant Neratinib Added To Standard Therapy In Patients With Her2-Positive Or Hr-Positive/Her2-Negative Inflammatory Breast Cancer (Including Stage Iii And Iv Disease), Bora Lim, Angela Marx, Megumi Kai, Angela Alexander, Roland Bassett, Wencai Ma, Jie Willey, Huiming Sun, Azadeh Nasrazadani, Mohammad M Mohammad, Jianhua Zhang, Anthony Lucci, Susie X Sun, Michael C Stauder, Gary J Whitman, Huong Le-Petross, Vicente Valero, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Inflammatory breast cancer (IBC) is rare but aggressive, characterized by the rapid onset of diffuse skin erythema, edema, tenderness, induration, and fast metastasis. Both hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+) are associated with inferior response after neoadjuvant systemic therapy (NAST) compared to non-IBC. Despite multimodal treatment approaches, the 3-year overall survival rate for stage III IBC remains low at approximately 74%, around 10% lower than the 83% for non-IBC.

Objectives: To evaluate whether the addition of neratinib, an irreversible pan-ErbB receptor small molecule tyrosine kinase inhibitor, improves the rate of pathological complete response in …

Changes In Functional Connectivity Are Associated With Functional Independence In The Early Postoperative Period Following Awake Surgical Resection Of Language-Eloquent Glioma, Kyle R Noll, Evan D Bander, Henry S Chen, Mariana Bradshaw, Jeffrey S Wefel, Vinodh A Kumar, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.

Methods: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain …