Life Sciences Commons^™

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Targetable Vulnerability Of Deregulated Foxm1/Plk1 Signaling Axis In Diffuse Large B Cell Lymphoma, Fang Yu, Hua He, Loretta J Nastoupil, Zijun Y Xu-Monette, Ky Pham, Guang Chen, C Cameron Yin, Dongfeng Tan, Yaling Yang, Shimin Hu, Ken H Young, Lan V Pham, M James You

Faculty, Staff and Student Publications

FOXM1 is a transcription factor that controls cell cycle regulation, cell proliferation, and differentiation. Overexpression of FOXM1 has been implicated in various cancer types. However, the activation status and functional significance of FOXM1 in diffuse large B cell lymphoma (DLBCL) have not been well investigated. Using proteomic approaches, we discovered that the protein expression levels of FOXM1 and PLK1 were positively correlated in DLBCL cell lines and primary DLBCL. Expression levels of FOXM1 and PLK1 mRNAs were also significantly higher in DLBCL than in normal human B cells and could predict poor prognosis of DLBCL, particularly in patients with germinal …

Increasing Referral Of At-Risk Women For Genetic Counseling And Brca Testing Using A Screening Tool In A Community Breast Imaging Center, Banu K Arun, Susan K Peterson, Lilian E Sweeney, Rachel D Bluebond, Rebecca S S Tidwell, Anne C Kushwaha

Faculty, Staff and Student Publications

BACKGROUND: Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals.

METHODS: A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling.

RESULTS: A total of 34,851 patients were screened during the study period, and 1246 …

Automated Segmentation Of Colorectal Liver Metastasis And Liver Ablation On Contrast-Enhanced Ct Images, Brian M Anderson, Bastien Rigaud, Yuan-Mao Lin, A Kyle Jones, Hynseon Christine Kang, Kristy K Brock

Faculty, Staff and Student Publications

Objectives: Colorectal cancer (CRC), the third most common cancer in the USA, is a leading cause of cancer-related death worldwide. Up to 60% of patients develop liver metastasis (CRLM). Treatments like radiation and ablation therapies require disease segmentation for planning and therapy delivery. For ablation, ablation-zone segmentation is required to evaluate disease coverage. We hypothesize that fully convolutional (FC) neural networks, trained using novel methods, will provide rapid and accurate identification and segmentation of CRLM and ablation zones.

Methods: Four FC model styles were investigated: Standard 3D-UNet, Residual 3D-UNet, Dense 3D-UNet, and Hybrid-WNet. Models were trained on 92 patients from …

A Narrative Review On Invasive Brain Stimulation For Treatment-Resistant Depression, Manoj P Dandekar, Alexandre P Diaz, Ziaur Rahman, Ritele H Silva, Ziad Nahas, Sudhakar Selvaraj, Marsal Sanches, Jair C Soares, Patricio Riva-Posse, Joao Quevedo

Faculty, Staff and Student Publications

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic …

Head-Mounted Digital Metamorphopsia Suppression As A Countermeasure For Macular-Related Visual Distortions For Prolonged Spaceflight Missions And Terrestrial Health, Joshua Ong, Nasif Zaman, Ethan Waisberg, Sharif Amit Kamran, Andrew G Lee

Faculty, Staff and Student Publications

During long-duration spaceflight, astronauts are exposed to various risks including spaceflight-associated neuro-ocular syndrome, which serves as a risk to astronaut vision and a potential physiological barrier to future spaceflight. When considering exploration missions that may expose astronauts to longer periods of microgravity, radiation exposure, and natural aging processes during spaceflight, more severe changes to functional vision may occur. The macula plays a critical role in central vision and disruptions to this key area in the eye may compromise functional vision and mission performance. In this article, we describe the development of a countermeasure technique to digitally suppress monocular central visual …

Quaking But Not Parkin Is The Major Tumor Suppressor In 6q Deleted Region In Glioblastoma, Fatma Betul Aksoy Yasar, Takashi Shingu, Daniel B Zamler, Mohammad Fayyad Zaman, Derek Lin Chien, Jiangong Ren

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a high-grade, aggressive brain tumor with dismal median survival time of 15 months. Chromosome 6q (Ch6q) is a hotspot of genomic alterations, which is commonly deleted or hyper-methylated in GBM. Two neighboring genes in this region, QKI and PRKN have been appointed as tumor suppressors in GBM. While a genetically modified mouse model (GEMM) of GBM has been successfully generated with Qk deletion in the central nervous system (CNS), in vivo genetic evidence supporting the tumor suppressor function of Prkn has not been established. In the present study, we generated a mouse model with Prkn-null allele …

Multiagent Chemotherapy And Stereotactic Body Radiation Therapy In Patients With Unresectable Pancreatic Adenocarcinoma: A Prospective Nonrandomized Controlled Trial, Colin S Hill, Lauren Rosati, Hao Wang, Hua-Ling Tsai, Jin He, Daniel A Laheru, Shuchi Sehgal, Vincent Bernard, Dung T Le, Timothy M Pawlik, Matthew J Weiss, Amol K Narang, Joseph M Herman

Faculty, Staff and Student Publications

PURPOSE: In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.

METHODS AND MATERIALS: This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between …

Editorial: The Role Of The Igf Axis In Tumorigenesis And Cancer Treatment: From Genes To Metabolites, Guo Mengzhe, Xie Shanshan, Zhao Di, Wu Shihua

Faculty, Staff and Student Publications

No abstract provided.

The Potential Of Biology-Guided Radiation Therapy In Thoracic Cancer: A Preliminary Treatment Planning Study, Steven N Seyedin, Rostem Bassalow, Osama R Mawlawi, Lehendrick M Turner, Roshal R Patel, Oluwaseyi M Oderinde, Cody A Wages, Peter D Olcott, Joe Y Chang, Peter A Balter, James W Welsh

Faculty, Staff and Student Publications

PURPOSE: We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.

METHODS: Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).

RESULTS: For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT …

Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Line Moi, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen

Faculty, Staff and Student Publications

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, …

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

Disruption Of Growth Hormone Receptor Signaling Abrogates Hepatocellular Carcinoma Development, Abedul Haque, Vishal Sahu, Jamie Lynne Lombardo, Lianchun Xiao, Bhawana George, Jeffrey S Morris, John J Kopchick, Ahmed O Kaseb, Hesham M Amin

Faculty, Staff and Student Publications

Introduction: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancers. It is an aggressive neoplasm with dismal outcome because most of the patients present with an advanced-stage disease, which precludes curative surgical options. Therefore, these patients require systemic therapies that typically induce small improvements in overall survival. Hence, it is crucial to identify new and promising therapeutic targets for HCC to improve the current outcome. The liver is a key organ in the signaling cascade triggered by the growth hormone receptor (GHR). Previous studies have shown that GHR signaling stimulates the proliferation and regeneration of liver cells …

Glioma And The Gut-Brain Axis: Opportunities And Future Perspectives, Antonio Dono, Jack Nickles, Ana G Rodriguez-Armendariz, Braden C Mcfarland, Nadim J Ajami, Jennifer A Wargo

Faculty, Staff and Student Publications

The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome …

Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Ren Zhang, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian

Faculty, Staff and Student Publications

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.

Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h …

A Multicenter Study Of Icu Resource Utilization In Pediatric, Adolescent And Young Adult Patients Post Car-T Therapy, Dristhi Ragoonanan, Saleh Bhar, Gopi Mohan, Fernando Beltramo, Sajad J Khazal, Clark Andersen, Sattva S Neelapu, Elizabeth Shpall, Cristina Gutierrez, Priti Tewari, Basirat Shoberu, Aimee Talleur, David Mccall, Cesar Nunez, Branko Cuglievan, Francesco Paolo Tambaro, Demetrios Petropoulos, Hisham Abdel-Azim, Kris M Mahadeo

Faculty, Staff and Student Publications

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging. In this multicenter study of ALL patients admitted for anti-leukemia therapy, who required pediatric intensive care (ICU) support (n = 205), patients receiving tisagenlecleucel (n = 39) were compared to those receiving conventional chemotherapy (n = 166). The median time to ICU transfer was 6 (0-43) versus 1 (0-116) days, respectively …

Evaluation Of Deep Learning-Based Multiparametric Mri Oropharyngeal Primary Tumor Auto-Segmentation And Investigation Of Input Channel Effects: Results From A Prospective Imaging Registry, Kareem A Wahid, Sara Ahmed, Renjie He, Lisanne V Van Dijk, Jonas Teuwen, Vivian Salama, Travis Salzillo, Cem Dede, Nicolette Taku, Stephen Y Lai, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background/purpose: Oropharyngeal cancer (OPC) primary gross tumor volume (GTVp) segmentation is crucial for radiotherapy. Multiparametric MRI (mpMRI) is increasingly used for OPC adaptive radiotherapy but relies on manual segmentation. Therefore, we constructed mpMRI deep learning (DL) OPC GTVp auto-segmentation models and determined the impact of input channels on segmentation performance.

Materials/methods: GTVp ground truth segmentations were manually generated for 30 OPC patients from a clinical trial. We evaluated five mpMRI input channels (T2, T1, ADC, Ktrans, Ve). 3D Residual U-net models were developed and assessed using leave-one-out cross-validation. A baseline T2 model was compared to mpMRI models (T2 + T1, …

Anatomy And Function Of Ventral Tegmental Area Glutamate Neurons, Jing Cai, Qingchun Tong

Faculty, Staff and Student Publications

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire …

Granuloma Annulare: An Updated Review Of Epidemiology, Pathogenesis, And Treatment Options, Tejas P Joshi, Madeleine Duvic

Faculty, Staff and Student Publications

Granuloma annulare (GA) is an inflammatory granulomatous skin disease that can be localized (localized GA) or disseminated (generalized GA), with patch, perforating, and subcutaneous subtypes being less common variants of this benign condition. Recently, new research has emerged that further elucidates GA epidemiology and etiopathogenesis; importantly, new therapeutic options for GA have also been described, although there remains a paucity of randomized controlled studies. In this review, we summarize recent updates on GA epidemiology and etiopathogenesis and offer an updated review of the therapeutic options for GA currently reported in the literature. We hope that the current review galvanizes randomized …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Siwen Hu-Lieskovan, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Deep-Learning-Based Generation Of Synthetic 6-Minute Mri From 2-Minute Mri For Use In Head And Neck Cancer Radiotherapy, Kareem A Wahid, Jiaofeng Xu, Dina El-Habashy, Yomna Khamis, Moamen Abobakr, Nicolette O' Connell, Sara Ahmed, Christina Setareh Sharafi, Kathryn Preston, Travis C Salzillo, Abdallah S R Mohamed, Renjie He, Nathan Cho, John Christodouleas, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background: Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images.

Methods: We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and …

Head And Neck Cancer Primary Tumor Auto Segmentation Using Model Ensembling Of Deep Learning In Pet/Ct Images, Mohamed A Naser, Kareem A Wahid, Lisanne V Van Dijk, Renjie He, Moamen Abobakr Abdelaal, Abdallah S R Mohamed

Faculty, Staff and Student Publications

Auto-segmentation of primary tumors in oropharyngeal cancer using PET/CT images is an unmet need that has the potential to improve radiation oncology workflows. In this study, we develop a series of deep learning models based on a 3D Residual Unet (ResUnet) architecture that can segment oropharyngeal tumors with high performance as demonstrated through internal and external validation of large-scale datasets (training size = 224 patients, testing size = 101 patients) as part of the 2021 HECKTOR Challenge. Specifically, we leverage ResUNet models with either 256 or 512 bottleneck layer channels that demonstrate internal validation (10-fold cross-validation) mean Dice similarity coefficient …

A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson

Faculty, Staff and Student Publications

The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. …

Semiparametric Copula-Based Regression Modeling Of Semi-Competing Risks Data, Hong Zhu, Yu Lan, Jing Ning, Yu Shen

Faculty, Staff and Student Publications

Semi-competing risks data often arise in medical studies where the terminal event (e.g., death) censors the non-terminal event (e.g., cancer recurrence), but the non-terminal event does not prevent the subsequent occurrence of the terminal event. This article considers regression modeling of semi-competing risks data to assess the covariate effects on the respective non-terminal and terminal event times. We propose a copula-based framework for semi-competing risks regression with time-varying coefficients, where the dependence between the non-terminal and terminal event times is characterized by a copula and the time-varying covariate effects are imposed on two marginal regression models. We develop a two-stage …

Residual Cancer Burden After Neoadjuvant Chemotherapy And Long-Term Survival Outcomes In Breast Cancer: A Multicentre Pooled Analysis Of 5161 Patients, Christina Yau, Marie Osdoit, Marieke Van Der Noordaa, Sonal Shad, Jane Wei, Anne-Sophie Hamy, Fabien Reyal, Gabe S Sonke, Tessa G Steenbruggen, Maartje Van Seijen, Jelle Wesseling, Miguel Martín, Maria Del Monte-Millán, Sara López-Tarruella, Judy C Boughey, Matthew P Goetz, Tanya Hoskin, Rebekah Gould, Vicente Valero, Stephen B Edge, Jean E Abraham, John M S Bartlett, Carlos Caldas, Janet Dunn, Helena Earl, Larry Hayward, Louise Hiller, Elena Provenzano, Stephen-John Sammut, Jeremy S Thomas, David Cameron, Ashley Graham, Peter Hall, Lorna Mackintosh, Fang Fan, Andrew K Godwin, Kelsey Schwensen, Priyanka Sharma, Angela M Demichele, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura J Van 'T Veer, Laura J Esserman, W Fraser Symmans

Faculty, Staff and Student Publications

Background: Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.

Methods: In this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, …

Allogeneic Hematopoietic Cell Transplantation For Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (Bpdcn), Qaiser Bashir, Denái R Milton, Uday R Popat, Partow Kebriaei, Chitra Hosing, Katayoun Rezvani, Betul Oran, Samer A Srour, Neeraj Y Saini, Amanda L Olson, Sairah Ahmed, Gheath Al-Atrash, Gabriela Rondon, Marina Y Konopleva, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Naveen Pemmaraju

Faculty, Staff and Student Publications

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Michael A Curran, Charles David James, Amy B Heimberger

Faculty, Staff and Student Publications

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …

Donor Selection For Kir Alloreactivity Is Associated With Superior Survival In Haploidentical Transplant With Ptcy, Jun Zou, Piyanuch Kongtim, Samer A Srour, Uri Greenbaum, Johannes Schetelig, Henning Baldauf, Supawee Saengboon, Yudith Carmazzi, Gabriela Rondon, Qing Ma, Katayoun Rezvani, Elizabeth J Shpall, Richard E Champlin, Stefan O Ciurea, Kai Cao

Faculty, Staff and Student Publications

With the continuous increase in the use of haploidentical donors for transplantation, the selection of donors becomes increasingly important. Haploidentical donors have been selected primarily based on clinical characteristics, while the effects of killer cell immunoglobulin-like receptors (KIRs) on outcomes of haploidentical-hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) remain inconclusive. The present study aimed to thoroughly evaluate the effect of KIRs and binding ligands assessed by various models, in addition to other patient/donor variables, on clinical outcomes in haplo-HSCT. In a cohort of 354 patients undergoing their first haplo-HSCT, we found that a higher Count Functional inhibitory KIR …

Establishment And Validation Of Pre-Therapy Cervical Vertebrae Muscle Quantification As A Prognostic Marker Of Sarcopenia In Patients With Head And Neck Cancer, Brennan Olson, Jared Edwards, Catherine Degnin, Nicole Santucci, Michelle Buncke, Yiyi Chen, Mathew Geltzeiler, Aaron J Grossberg, Daniel Clayburgh

Faculty, Staff and Student Publications

Background: Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC.

Methods: This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT …

Application Of Artificial Intelligence To Plasma Metabolomics Profiles To Predict Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Ehsan Irajizad, Ranran Wu, Jody Vykoukal, Eunice Murage, Rachelle Spencer, Stacy Moulder, Bora Lim, Jennifer Litton, Debu Tripathym, Vicente Valero, Senthil Damodaran, Gaiane M Rauch, Beatriz Adrada, Rosalind Candelaria, Jason B White, Abenaa Brewster, Banu Arun, James P Long, Kim Anh Do, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied …