Digital Commons Network^™

Endovascular Interventions In Cancer Patients With Compromise Of The Mediastinal Vasculature: A Review, Steven Yevich, Nicolas Cardenas, Rahul Sheth, Joshua Kuban, Milan Patel, Ketan Shah, Koustav Pal, Stephen R Chen, Alda Tam

Faculty, Staff and Student Publications

The mediastinal vasculature can be affected by various etiologies in cancer patients. Both direct and indirect sequela of cancer may result in life-threatening clinical presentations. Tumor growth may cause vessel narrowing and decreased blood flow from either extrinsic mass effect, invasion into the vascular wall, or tumor thrombus within the lumen. In addition, cancer patients are predisposed to indirect sequela to the mediastinal vasculature from an increased risk of benign thromboembolic events, tumor thrombus, or iatrogenic complications during cancer treatments. Benign thrombus may result in partial or complete occlusion of the superior vena cava (SVC) or pulmonary artery. Vascular damage …

A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer

Faculty, Staff and Student Publications

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing …

Research Hot Spots And Trends In Endocrine-Related Adverse Events Caused By Immune Checkpoint Inhibitors: A Bibliometric Analysis And Visualization Research, Jun Zhao, Guangwei Liu, Xue Yang, Chuanzhou Zhang, Bing Han, Man Jiang

Faculty, Staff and Student Publications

Background: In recent years, with the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment, the toxicity associated with immunotherapy of ICIs has attracted more attention from scholars. Endocrine toxicity is the most likely immune-related adverse events (irAEs) and is often irreversible, posing a significant clinical treatment challenge.

Methods: In this study, bibliometric methods were used to analyze relevant literature in screening endocrine-related adverse events caused by ICIs in the Web of Science core collection database (WoSCC) and to summarize the status, research hot spots, and future trends in this field.

Results: 321 countries, 297 institutions, 365 authors, and …

Camrelizumab Combined With Apatinib And Nanoparticle Albumin-Bound Paclitaxel In Lung Adenocarcinoma (Capap-Lung): A Single-Arm Phase Ii Study, Xingxiang Pu, Gen Lin, Maoliang Xiao, Jie Lin, Qianzhi Wang, Yi Kong, Xuejun Yan, Fang Xu, Yan Xu, Jia Li, Kang Li, Bolin Chen, Xiaoping Wen, Yali Tan, Fengzhuo Cheng, Kangle Zhu, Na Li, Lin Wu

Faculty, Staff and Student Publications

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma.

Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma …

Knowledge Mapping Of Anaplastic Thyroid Cancer Treatments: A Bibliometric Analysis (2000–2023), Shiqiang Liu, Xingmin Yan, Yalong Yang, Yun Xia, Panshi Zhang

Faculty, Staff and Student Publications

Context: Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature.

Methodology: A systematic search was …

Combining Egfr And Kras G12c Inhibitors For Kras G12c Mutated Advanced Colorectal Cancer, Hirotaka Miyashita, David S Hong

Faculty, Staff and Student Publications

KRAS is a commonly mutated gene in advanced colorectal cancer (CRC). Recently, inhibitors of KRAS G12C were developed and have shown promising efficacy for KRAS G12C mutated non-small cell lung cancer. However, KRAS G12C inhibitor monotherapy has not demonstrated excellent efficacy for KRAS G12C mutated advanced CRC due to multiple resistance mechanisms, especially receptor tyrosine kinase (RTK) signaling activation. To overcome this resistance mechanism, various combinations of epithelial growth factor receptor (EGFR) and KRAS G12C inhibitors, including panitumumab plus sotorasib, have been investigated in clinical trials. The combination of EGFR and KRAS G12C inhibitors for KRAS G12C mutated CRC demonstrated …

Sotorasib With Panitumumab In Chemotherapy-Refractory Kras G12c-Mutated Colorectal Cancer: A Phase 1b Trial, Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger, Toshiki Masuishi, Edward J Kim, Christine M Bestvina, Scott Kopetz, Gerald S Falchook, Corey Langer, John Krauss, Sonam Puri, Panli Cardona, Emily Chan, Tracy Varrieur, Lata Mukundan, Abraham Anderson, Qui Tran, David S Hong

Faculty, Staff and Student Publications

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRAS

Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby

Faculty, Staff and Student Publications

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17).

METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, …

Exploring Measurement Tools Used To Assess Knowledge, Attitudes, And Perceptions Of Pregnant Women Toward Prenatal Screening: A Systematic Review, Lea Sacca, Yasmine Zerrouki, Sara Burgoa, Goodness Okwaraji, Ashlee Li, Shaima Arshad, Maria Gerges, Stacey Tevelev, Sophie Kelly, Michelle Knecht, Panagiota Kitsantas, Robert Hunter, Laurie Scott, Alexis Piccoli Reynolds, Gabriela Colon, Michele Retrouvey

Faculty, Staff and Student Publications

There is a lack of standardized measurement tools globally to assess knowledge, attitudes, and perceptions of expecting women toward prenatal screening. The purpose of this systematic review was to identify reasons women pursue or decline prenatal screening and compare the strengths and limitations of available measurement tools used to assess pregnant women's perceptions, knowledge, and attitudes toward prenatal screening. This review followed the five-step York methodology by Arksey and O'Malley and incorporated recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist for the extraction, analysis, and presentation of results. The five steps consisted of: (1) identification of …

From Transcriptomics To Digital Twins Of Organ Function, Jens Hansen, Abhinav R Jain, Philip Nenov, Peter N Robinson, Ravi Iyengar

Faculty, Staff and Student Publications

Cell level functions underlie tissue and organ physiology. Gene expression patterns offer extensive views of the pathways and processes within and between cells. Single cell transcriptomics provides detailed information on gene expression within cells, cell types, subtypes and their relative proportions in organs. Functional pathways can be scalably connected to physiological functions at the cell and organ levels. Integrating experimentally obtained gene expression patterns with prior knowledge of pathway interactions enables identification of networks underlying whole cell functions such as growth, contractility, and secretion. These pathways can be computationally modeled using differential equations to simulate cell and organ physiological dynamics …

Egfr, Hla-G, Cd70, C-Met, And Ny-Eso1 As Potential Biomarkers In High Grade Epithelial Ovarian Carcinoma, Duc Vo, Yan Liu, Anil K Sood, Katy Rezvani, Amir A Jazaeri, Jinsong Liu

Faculty, Staff and Student Publications

High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of …

Expert-Centered Evaluation Of Deep Learning Algorithms For Brain Tumor Segmentation, Katharina V Hoebel, Christopher P Bridge, Sara Ahmed, Oluwatosin Akintola, Caroline Chung, Raymond Y Huang, Jason M Johnson, Albert Kim, K Ina Ly, Ken Chang, Jay Patel, Marco Pinho, Tracy T Batchelor, Bruce R Rosen, Elizabeth R Gerstner, Jayashree Kalpathy-Cramer

Faculty, Staff and Student Publications

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of …

Nontuberculosis Mycobacteria (Ntm) Infections In Patients With Leukemia: A Single Center Case Series, Jennifer Marvin-Peek, Koji Sasaki, Dimitrios P Kontoyiannis, Javier Adachi, Maro Ohanian, Koichi Takahashi, Ghayas C Issa, Steven Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with …

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …

Canadian French Translation And Validation Of The Neck Dissection Impairment Index: A Quality Of Life Measure For The Surgical Oncology Population, Michel Khoury, William Guertin, Cameo Hao, Mikhail Saltychev, Tareck Ayad, Eric Bissada, Apostolos Christopoulos, Sami Moubayed, Marie-Jo Olivier, Douglas Chepeha, Stephen Y Lai, Anastasios Maniakas

Faculty, Staff and Student Publications

BACKGROUND: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French.

METHODS: A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session …

Differing Impacts Of The Covid-19 Pandemic On Farmers And Intermediaries: Insights Into The Ecuadorian Cocoa Value Chain, Guillermo Zambrano, Lina M Tennhardt, Moritz Egger, Karen Ramírez, Adriana Santos, Byron Moyano, Michael Curran

Faculty, Staff and Student Publications

The COVID-19 pandemic generated diverse impacts and responses in agricultural value chains worldwide. Cocoa is a key crop for Ecuadorian exports, and the analysis of effects the pandemic had on value chain actors contributes to the understanding of their individual capacities to coping with a major shock. The purpose of this study was to assess the number and severity of impacts and responses implemented by two links in the cocoa value chain to the pandemic, based on a survey of 158 cocoa farmers and 52 cocoa intermediaries from the main cocoa-producing provinces of the northern coast of Ecuador in 2021. …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Early And Rapid Development Of Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation, Jacqueline S Dickey, Burton F Dickey, Amin M Alousi, Richard E Champlin, Ajay Sheshadri

Faculty, Staff and Student Publications

Bronchiolitis obliterans (BO) is a form of graft-versus-host disease (GVHD) in the lung and manifests as moderate to severe airflow obstruction after hematopoietic stem cell transplantation (HCT). New-onset airflow obstruction on spirometry is considered diagnostic of bronchiolitis obliterans syndrome (BOS). BOS affects about 5% of all HCT recipients. In general, BO is thought of as a late complication of HCT, usually occurring after day 100 post-transplantation. However, the onset of airflow obstruction can be rapid and is most often irreversible even with treatment. We describe a patient who rapidly developed severe airflow obstruction less than one month after transplantation following …

Epigallocatechin Gallate Regulates The Myeloid-Specific Transcription Factor Pu1 In Macrophages, Manjula Karpurapu, Kavita Kumari Kakarala, Sangwoon Chung, Yunjuan Nie, Amritendu Koley, Patrick Dougherty, John W Christman

Faculty, Staff and Student Publications

Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.1 in macrophages ameliorated LPS-induced acute lung injury (ALI) in bone marrow chimera mice. Inhibitors that block the transcriptional activity of PU.1 in macrophages have the potential to mitigate the pathophysiology of LPS-induced ALI. However, complete inactivation of PU.1 gene disrupts normal myelopoiesis. Although the green tea polyphenol Epigallocatechin gallate (EGCG) has been shown to regulate inflammatory genes in various cell types, it is not known if EGCG alters the transcriptional activity of PU.1 protein. Using Schrodinger Glide docking, we have …

Suppression Of Il-1Β Promotes Beneficial Accumulation Of Fibroblast-Like Cells In Atherosclerotic Plaques In Clonal Hematopoiesis, Trevor P Fidler, Andrew Dunbar, Eunyoung Kim, Brian Hardaway, Jessica Pauli, Chenyi Xue, Sandra Abramowicz, Tong Xiao, Kavi O'Connor, Nadja Sachs, Nan Wang, Lars Maegdefessel, Ross Levine, Muredach Reilly, Alan R Tall

Faculty, Staff and Student Publications

Clonal hematopoiesis (CH) is an independent risk factor for atherosclerotic cardiovascular disease. Murine models of CH suggest a central role of inflammasomes and IL-1β in accelerated atherosclerosis and plaque destabilization. Here we show using single-cell RNA sequencing in human carotid plaques that inflammasome components are enriched in macrophages, while the receptor for IL-1β is enriched in fibroblasts and smooth muscle cells (SMCs). To address the role of inflammatory crosstalk in features of plaque destabilization, we conducted SMC fate mapping in Ldlr-/- mice modeling Jak2VF or Tet2 CH treated with IL-1β antibodies. Unexpectedly, this treatment minimally affected SMC differentiation, …

Microbiota Restoration Therapies For Recurrent Clostridioides Difficile Infection Reach An Important New Milestone, Herbert L Dupont, Andrew W Dupont, Glenn S Tillotson

Faculty, Staff and Student Publications

Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce …

Loss Of The Auxiliary Α 2Δ1 Voltage-Sensitive Calcium Channel Subunit Impairs Bone Formation And Anabolic Responses To Mechanical Loading, Madison M Kelly, Karan Sharma, Christian S Wright, Xin Yi, Perla C Reyes Fernandez, Aaron T Gegg, Taylor A Gorrell, Megan L Noonan, Ahmed Baghdady, Jacob A Sieger, Annette C Dolphin, Stuart J Warden, Padmini Deosthale, Lilian I Plotkin, Uma Sankar, Julia M Hum, Alexander G Robling, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α2δ1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1, the gene encoding α2δ1. Dual-energy X-ray absorptiometry and microcomputed tomography imaging demonstrated that deletion of α2δ1 diminished bone mineral content and density in both male and female …

Human Minor Salivary Glands: A Readily Available Source Of Salivary Stem/Progenitor Cells For Regenerative Applications, Caitlynn M L Barrows, Danielle Wu, Simon Young, Mary C Farach-Carson

Faculty, Staff and Student Publications

Resident stem/progenitor cells within the secretory salivary glands offer a potential therapeutic resource for use in the regeneration of salivary glands needed to restore saliva production in patients with chronic xerostomia, or dry mouth. Methods were developed previously to isolate human stem/progenitor cells (hS/PCs) from major salivary glands (parotid/submandibular). Abundant minor salivary glands located in readily accessible locations in the oral cavity and lip could provide an additional valuable therapeutic resource. An advantage of this cell resource is that these minor glands about the size of grape seeds can be harvested from healthy donors using minimally invasive surgical procedures. The …

Image-Guided Deployment And Monitoring Of A Novel Tungsten Nanoparticle-Infused Radiopaque Absorbable Inferior Vena Cava Filter In A Swine Model, Erin Marie San Valentin, Jossana A Damasco, Marvin Bernardino, Karem A Court, Biana Godin, Gino Martin Canlas, Adam Melancon, Gouthami Chintalapani, Megan C Jacobsen, William Norton, Rick R Layman, Natalie Fowlkes, Stephen R Chen, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

PURPOSE: To improve radiopacity of radiolucent absorbable poly-p-dioxanone (PPDO) inferior vena cava filters (IVCFs) and demostrate their effectiveness in clot-trapping ability.

MATERIALS AND METHODS: Tungsten nanoparticles (WNPs) were incorporated along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of WNPs. The physicochemical and in vitro and in vivo imaging properties of PPDO IVCFs with WNPs with single-polymer PHB (W-P) were compared with those of WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB).

RESULTS: In vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the …

The Contribution Of Dna Ligase 4 Polymorphisms To Colorectal Cancer, Yang Deng, Tao-Wei Ke, Te-Cheng Yueh, Yu-Ting Chin, Yun-Chi Wang, Yi-Chih Hung, Mei-Chin Mong, Ya-Chen Yang, Wen-Tzu Wu, Wen-Shin Chang, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: While numerous biomarkers associated with genetic susceptibility to colorectal cancer (CRC) have been identified and validated through epidemiological studies, the specific influence of DNA ligase 4 (Lig4) genotypes remains unexplored. This study aimed to elucidate the hitherto unexamined relationship between Lig4 genotypes and CRC risk.

Materials and methods: The genotypes of Lig4 rs1805388 were determined applying the polymerase chain reaction-restriction fragment length polymorphism methodology. The potential association between these genotypes and CRC risk was assessed in a Taiwanese population comprising 362 CRC cases and an equal number of age- and sex-matched controls.

Results: In the genotypic analysis, the distribution …

Non-Homologous End-Joining Genotype, Mrna Expression, And Dna Repair Capacity In Childhood Acute Lymphocytic Leukemia, Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Yun-Chi Wang, Pei-Chen Hsu, Jie-Long He, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.

Materials and methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation …

Case Report: Early Acute Kidney Failure In An 11-Year-Old Boy With Dent Disease Type 1, Nicolette Murphey, Craig Authement, Paul Hillman, Samhar I Al-Akash, Kate Richardson

Faculty, Staff and Student Publications

Dent disease type 1 (Dent 1) is a rare X-linked genetic condition which impacts kidney function and is caused by pathogenic variants in CLCN5. Affected males typically develop low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and other symptoms. Kidney failure often occurs between the third to fifth decade of life. Here, we report an 11-year-old boy with Dent 1 and a severe kidney disease phenotype. The patient presented with flank pain, nocturnal enuresis, foamy urine, and increased urinary frequency. He was found to have nephrotic-range proteinuria, without hypoalbuminemia, and a significantly decreased estimated glomerular filtration rate at presentation. Further, he …

Her4 And Egfr Activate Cell Signaling In Nrg1 Fusion-Driven Cancers: Implications For Her2-Her3-Specific Versus Pan-Her Targeting Strategies, Hibiki Udagawa, Monique B Nilsson, Jacqulyne P Robichaux, Junqin He, Alissa Poteete, Hong Jiang, Simon Heeke, Yasir Y Elamin, Yuji Shibata, Shingo Matsumoto, Kiyotaka Yoh, Shogo Okazaki, Takashi Masuko, Igor Odintsov, Romel Somwar, Marc Ladanyi, Koichi Goto, John V Heymach

Faculty, Staff and Student Publications

Introduction: NRG1 gene fusions are clinically actionable alterations identified in NSCLC and other tumors. Previous studies have reported that NRG1 fusions signal through HER2 and HER3 but, thus far, strategies targeting HER3 specifically or HER2-HER3 signaling have exhibited modest activity in patients with NSCLC bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers is not fully understood.

Methods: We investigated the role of HER4 and EGFR-HER3 signaling in NRG1 fusion-positive cancers using Ba/F3 models engineered to express various HER family members in …

Establishment Of A Brain Tumor Consortium Of Africa: Advancing Collaborative Research And Advocacy For Brain Tumors In Africa, Lateef A Odukoya, Kwadwo Darko, Francis Zerd, Nathalie C Ghomsi, Gloria Kabare, David O Kamson, Jeanette E Eckel-Passow, Robert B Jenkins, Gaspar J Kitange, Andrea O Akinjo, Kabir B Badmos, Olufemi Bankole, Olufemi E Idowu, Claire Karekezi, Elias Edrick, Chukwuyem Ekhator, Victoria M Katasi, Desmond A Brown, Jason Huse, Henry Llewellyn, Margreth Magambo, Michael Magoha, Umaru Barrie, Advera Ngaiza, Arsene D Nyalundja, Minda Okemwa, Lawrence Osei-Tutu, Bernard Petershie, W Elorm Yevudza, Charles C Anunobi, Liadi Tiamiyu, Gbetoho Fortuné Gankpe, Kashaigili Heronima, Dominique Higgins, Kristin Schroeder, Teddy Totimeh, James Balogun, Beverly Cheserem, Arnold B Etame, Ekokobe Fonkem

Faculty, Staff and Student Publications

Background: Brain tumors represent a significant global health challenge, with rising incidence and mortality impacting individuals worldwide and contributing to cancer-related morbidity and mortality. In Africa, this burden is exacerbated by limited access to advanced diagnostics, treatment options, and multidisciplinary care, compounded by the absence of standardized cancer registration and tumor biobanking. The introduction of molecular diagnostics, as outlined in the 2021 World Health Organization central nervous system (CNS) tumor classification, adds complexity to brain tumor management, particularly in regions with scarce resources.

Methods: To address these issues, the Brain Tumor Consortium for Africa (BTCA) was established in 2023, bringing …

Circulating Cancer-Associated Macrophage-Like Cells And Macrophage-Related Cytokines In Obese Patients With Advanced Breast Cancer Who Undergo Neoadjuvant Chemotherapy, Toshiaki Iwase, Aaroh Parikh, Dong Wenli, Yu Shen, Daniel L Adams, Cha-Mei Tang, Evan N Cohen, James M Reuben, Tushaar Vishal Shrimanker, Sudpreeda Chainitikun, Kumiko Kida, Akshara Singareeka Raghavendra, Maryanne E Sapon, Onur Sahin, Anjali James, Nithya Sridhar, Ann H Klopp, Debasish Tripathy, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Cancer-associated macrophage-like cells (CAMLs) are rare, gigantic, and atypical circulating cells found exclusively in the peripheral blood of patients with solid cancers. Obesity-induced hypoxia attracts macrophages to the tumor microenvironment, where they contribute to establishing chronic inflammation, leading to cancer progression. We hypothesized that obese patients with advanced breast cancer may have CAML profiles different from those of nonobese patients, and these profiles may correlate with proinflammatory markers or other macrophage-related markers.

Methods: We prospectively collected 20 mL of peripheral blood from patients diagnosed with stage 2-4 breast cancer. We identified CAMLs using the CellSieve microfiltration system and in …