Digital Commons Network^™

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Student and Faculty Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

Targeting The Glutamine-Arginine-Proline Metabolism Axis In Cancer, Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu

Student and Faculty Publications

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy …

It’S About Time: Mitigating Cancer-Related Cognitive Impairments Through Findings From Computational Models Of The Wisconsin Card Sorting Task, Darren Haywood, Frank D. Baughman, Evan Dauer, Jennifer Haywood, Susan Rossell, Nicolas H. Hart

Research outputs 2022 to 2026

Background: Many cancer survivors experience cancer-related cognitive impairment (CRCI), often with significant negative consequences across various life domains. Emerging evidence suggests that allowing additional time to process information before acting may be a useful strategy for those with CRCI to mitigate some of its impacts. The Wisconsin Card Sorting Task (WCST), a measure of general cognition, has shown that for some cancer survivors, longer task completion time facilitates similar task performance outcomes to control populations concerning perseveration errors; a key performance metric of the WCST. However, assessing if this strategy may be useful, as well as determining for whom it …

Patient Experiences: A Qualitative Systematic Review Of Chemotherapy Adherence, Amineh Rashidi, Susma Thapa, Wasana Sandamali Kahawaththa Palliya Guruge, Shubhpreet Kaur

Research outputs 2022 to 2026

Adherence to chemotherapy treatment is recognized as a crucial health concern, especially in managing cancer patients. Chemotherapy presents challenges for patients, as it can lead to potential side effects that may adversely affect their mobility and overall function. Patients may sometimes neglect to communicate these side effects to health professionals, which can impact treatment management and leave their unresolved needs unaddressed. However, there is limited understanding of how patients’ experiences contribute to improving adherence to chemotherapy treatment and the provision of appropriate support. Therefore, gaining insights into patients’ experiences is crucial for enhancing the accompaniment and support provided during chemotherapy. …

Enhancing Circulatory Myokines And Extracellular Vesicle Uptake With Targeted Exercise In Patients With Prostate Cancer (The Myex Trial): A Single-Group Crossover Study, Jin Soo Kim, Dennis R. Taaffe, Daniel A. Galvão, Timothy D. Clay, Andrew D. Redfern, Elin S. Gray, Robert U. Newton

Research outputs 2022 to 2026

Introduction: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with …

Providing End-Of-Life Counseling: A Narrative Inquiry, Carol Hecht, Sibyl West

Adultspan Journal

This qualitative study aimed to address the gap in the research related to end-of-life counseling by exploring the experiences of counselors working with clients at end of life. While counseling literature and education are lacking regarding end of life, many counselors will work alongside clients approaching death. The purpose of this study was twofold: (a) to better understand the nuanced experiences of counselors providing end-of-life counseling and (b) to explore the supports and preparations helpful for counselors to provide end-of-life counseling. A narrative approach, using the Listening Guide (Gilligan, 2015), was employed to analyze and present the stories of three …

Considerations Of Medicare Telehealth Services With Older Adults, Sonah Kho, Amanda Dediego

Adultspan Journal

The onset of the COVID-19 pandemic set in motion a rapid expansion of mental health services offered via telehealth. With this rapid expansion came the need to examine how policy and practice should be shaped in a future where telehealth is considered common in counseling practice. For counselors to understand how to support older adult clients in using telehealth services, they must understand telehealth policy. Following the eligibility of licensed counselors to participate in Medicare, counselors need to stay abreast of regulatory changes regarding restrictions and regulations on use of telehealth for mental and behavioral health services, including video and …

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Unique Considerations In The Management Of Healthcare Among Fertile Women A Case Report On Chronic Myeloid Leukemia And Pregnancy, Hermione Yamyo Monie, Taha Al Hassan, Salomon Pardo Roca, Uchechi Ehiemua, Ramiro Leal

Research Colloquium

Background: With the overturning of Roe v. Wade, the management of women who are family planning has become more complex, highlighting the necessity for comprehensive and informed healthcare. This case report underscores the importance of holistic, interdisciplinary care for women with chronic conditions like Chronic Myeloid Leukemia (CML) who are planning for pregnancy. The novelty lies in the interplay between oncological treatment and reproductive health under current legal constraints.

Case Presentation: We present the case of a 32-year-old woman, G2P0010, with a history of CML and a previous spontaneous abortion. Initially believed to be in remission, she was started …

Utilization Of Pap Smears And Cervicovaginal Fluid For Early Ovarian Cancer Screening & Detection, Natasha Bell, Subhash C. Chauhan

Research Colloquium

Background: Ovarian cancer (OC) remains the gynecologic cancer with the highest mortality due to late-stage diagnosis, lack of effective screening tools, and nonspecific symptoms. This literature review evaluates the use of Pap smears and cervicovaginal fluids for early OC detection. This review explores their potential for detecting OC-specific biomarkers, mutations, proteomics, and methylation patterns from Pap smears and cervicovaginal fluids to investigate their effectiveness and utility as screening and diagnostic tools for OC.

Methods: A systematic PubMed search was conducted using keywords related to ovarian cancer diagnosis, Pap smears, early detection, cervical swabs, mutations, and methylation. Eligibility criteria focused on …

Oxidative Stress In Leukemia: A Double-Edged Sword, Alex Zuo, Anthony L. Alanis

Research Colloquium

Reactive oxygen species (ROS) play a crucial role in the pathogenesis and therapeutic resistance of acute myeloid leukemia (AML). AML cells exhibit heightened ROS levels compared to normal hematopoietic cells, primarily attributed to NOX2 activity. Alterations in ROS metabolism contribute to therapy resistance and relapse in AML, prompting investigations into ROS-targeting therapeutic strategies. Inhibition of mitochondrial fusion reduces ROS production, inducing cell cycle arrest at the G0/G1 transition, underscoring the regulatory role of mitochondrial dynamics in AML progression. Additionally, LNS8801, a G protein-coupled estrogen receptor agonist, induces ROS-mediated apoptosis via the endoplasmic reticulum stress pathway in AML cells, suggesting a …

Blast And Bursts: Unveiling Splenic Rupture In Blastic Plasmacytoid Dendritic Cell Neoplasia, Abdulahi Hassan, Matthew Simpson, Rahim Jiwani, Abigail Arrigo, Palgun Nisarga, Olukemi A. Esan, Anna Koget

Journal of Community Hospital Internal Medicine Perspectives

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare hematologic cancer, accounting for less than 1% of acute leukemias in the U.S. Diagnosis involves detecting markers like CD123, CD4, CD56, TCL1, and TCF4. Treatment typically involved acute leukemia therapies, but Tagraxofusp, a targeted therapy, was recently approved. Despite advancements, prognosis remains grim, with a median survival of around 1 year. Atraumatic splenic rupture (ASR) is a rare complication of this condition, with only five cases reported from 1994 to 2018. Here we present a case of BPDCN complicated by ASR. This case emphasizes the challenges of diagnosing and treating BPDCN, …

Viscous Vengeance: A Case Report Of Hyperviscosity Syndrome In Iga Lambda Multiple Myeloma, Afoma Onyechi, Jessica Ohemeng-Dapaah, Ayesha Kang, Alexandre Lacasse, Ranju Kunwor

Journal of Community Hospital Internal Medicine Perspectives

Multiple myeloma (MM) is a relatively uncommon neoplastic proliferation of monoclonal plasma cells. Common manifestations are related to infiltration of plasma cells into bones and other organs, causing an increased total serum protein concentration, hypercalcemia, kidney injury, and anemia. The most common type of MM is IgG Kappa, and the second most common type is the IgA subtype. Hyperviscosity (HVS) is a rare presentation of MM and management includes prompt plasmapheresis, resulting in significant reduction of serum viscosity and symptomatic relief. We present a case of IgA Lambda MM presenting with HVS.

The Scaffolding Function Of Lsd1 Controls Dna Methylation In Mouse Escs, Sandhya Malla, Kanchan Kumari, Carlos A García-Prieto, Jonatan Caroli, Anna Nordin, Trinh T T Phan, Devi Prasad Bhattarai, Carlos Martinez-Gamero, Eshagh Dorafshan, Stephanie Stransky, Damiana Álvarez-Errico, Paulina Avovome Saiki, Weiyi Lai, Cong Lyu, Ludvig Lizana, Jonathan D Gilthorpe, Hailin Wang, Simone Sidoli, Andre Mateus, Dung-Fang Lee, Claudio Cantù, Manel Esteller, Andrea Mattevi, Angel-Carlos Roman, Francesca Aguilo

Student and Faculty Publications

Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but …

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Student and Faculty Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Pancreatic Epithelial Il17/Il17ra Signaling Drives B7-H4 Expression To Promote Tumorigenesis, Susana Castro-Pando, Rian M Howell, Le Li, Marilina Mascaro, Erika Y Faraoni, Olivereen Le Roux, David Romanin, Virginia Tahan, Erick Riquelme, Yu Zhang, Jay K Kolls, James P Allison, Guillermina Lozano, Seyed J Moghaddam, Florencia Mcallister

Student and Faculty Publications

IL17 is required for the initiation and progression of pancreatic cancer, particularly in the context of inflammation, as previously shown by genetic and pharmacological approaches. However, the cellular compartment and downstream molecular mediators of IL17-mediated pancreatic tumorigenesis have not been fully identified. This study examined the cellular compartment required by generating transgenic animals with IL17 receptor A (IL17RA), which was genetically deleted from either the pancreatic epithelial compartment or the hematopoietic compartment via generation of IL17RA-deficient (IL17-RA-/-) bone marrow chimeras, in the context of embryonically activated or inducible Kras. Deletion of IL17RA from the pancreatic epithelial compartment, but not from …

Calibration Of A Novel Microdosimetry System For In Vitro Applications Of Actinide Radiopharmaceuticals, Lydia J. Wilson, Brian Miller, George Tabatadze, Firas Mourtada

Department of Radiation Oncology Posters

Background

• Alpha-emitting radionuclides show promise for targeted radiopharmaceutical therapy (TRT).
• High linear energy transfer and short range cause highly localized DNA damage for effective cancer cell eradication.
• However, distributions of radioactivity and absorbed dose on the cellular scale remain elusive.
• Progress toward understanding α-TRT radiobiologic response, evaluating novel α-TRT drug efficacy, and optimizing administration for personalized treatments will require knowledge of radioactivity and absorbed dose distributions.
• A novel real-time α camera, the ionizing radiation quantum imaging detector (iQID), has successfully mapped the microdistribution of α-emitting radionuclides in mouse and human tissues [1].

The Fibro-Adipogenic Progenitor Apod+Dcn+Llum+ Cell Population In Aggressive Carcinomas, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Student and Faculty Publications

We identified a progenitor cell population highly enriched in samples from invasive and chemo-resistant carcinomas, characterized by a well-defined multigene signature including APOD, DCN, and LUM. This cell population has previously been labeled as consisting of inflammatory cancer-associated fibroblasts (iCAFs). The same signature characterizes naturally occurring fibro-adipogenic progenitors (FAPs) as well as stromal cells abundant in normal adipose tissue. Our analysis of human gene expression databases provides evidence that adipose stromal cells (ASCs) are recruited by tumors and undergo differentiation into CAFs during cancer progression to invasive and chemotherapy-resistant stages.

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W Clemens, Terence M Myckatyn, Arianna Di Napoli, Andrew L Feldman, Elaine S Jaffe, Cara L Haymaker, Steven M Horwitz, Kelly K Hunt, Marshall E Kadin, Colleen M Mccarthy, Roberto N Miranda, H Miles Prince, Fabio Santanelli Di Pompeo, Sari D Holmes, Linda G Phillips

Student and Faculty Publications

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

Organ-Specific Dosimetry Following Radiopharmaceutical Therapy For Metastatic Prostate Cancer, Frank J. Arturi, Nilanjan Haldar, Shray Jain, Gia Nguyen, Jessie Dinome, Firas Mourtada, Lydia J. Wilson, Phd

Department of Radiation Oncology Posters

Introduction

• Radiopharmaceutical Therapy (RPT) uses radioactive agents to target cancer at the cellular level
• Lu-177 targeting prostate-specific membrane antigen (PSMA), known as 177Lu- PSMA-617, can be used to treat metastatic, castration-resistant prostate cancer (mCRPC)
• 177Lu-PSMA-617 treatments use a standard dose and treatment regimen for all patients
• Patients exhibit different side effects and tumor response during treatment

Detection Of Distant Relatedness In Biobanks To Identify Undiagnosed Cases Of Mendelian Disease As Applied To Long Qt Syndrome, Megan C Lancaster, Hung-Hsin Chen, M Benjamin Shoemaker, Matthew R Fleming, Teresa L Strickland, James T Baker, Grahame F Evans, Hannah G Polikowsky, David C Samuels, Chad D Huff, Dan M Roden, Jennifer E Below

Student and Faculty Publications

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this …

Mechanisms And Metabolic Consequences Of Adipocyte Progenitor Replicative Senescence, Tonghui Lin, Aftab Mohammad, Mikhail G Kolonin, Kristin L Eckel-Mahan

Student and Faculty Publications

In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Student and Faculty Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Donor Types And Outcomes Of Transplantation In Myelofibrosis: A Cibmtr Study, Tania Jain, Noel Estrada-Merly, M Queralt Salas, Soyoung Kim, Jakob Devos, Min Chen, Xi Fang, Rajat Kumar, Marcio Andrade-Campos, Hany Elmariah, Vaibhav Agrawal, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M Badawy, Karen Ballen, Amer Beitinjaneh, Vijaya Raj Bhatt, Christopher Bredeson, Zachariah Defilipp, Bhagirathbhai Dholaria, Nosha Farhadfar, Shatha Farhan, Arpita P Gandhi, Siddhartha Ganguly, Usama Gergis, Michael R Grunwald, Nada Hamad, Betty K Hamilton, Yoshihiro Inamoto, Madiha Iqbal, Omer Jamy, Mark Juckett, Mohamed A Kharfan-Dabaja, Maxwell M Krem, Deepesh P Lad, Jane Liesveld, Monzr M Al Malki, Adriana K Malone, Hemant S Murthy, Guillermo Ortí, Sagar S Patel, Attaphol Pawarode, Miguel-Angel Perales, Marjolein Van Der Poel, Olle Ringden, David A Rizzieri, Alicia Rovó, Bipin N Savani, Mary Lynn Savoie, Sachiko Seo, Melhem Solh, Celalettin Ustun, Leo F Verdonck, John R Wingard, Baldeep Wirk, Nelli Bejanyan, Richard J Jones, Taiga Nishihori, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, Vikas Gupta

Department of Medical Oncology Faculty Papers

We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched …

Meti: Deep Profiling Of Tumor Ecosystems By Integrating Cell Morphology And Spatial Transcriptomics, Jiahui Jiang, Yunhe Liu, Jiangjiang Qin, Jianfeng Chen, Jingjing Wu, Melissa P Pizzi, Rossana Lazcano, Kohei Yamashita, Zhiyuan Xu, Guangsheng Pei, Kyung Serk Cho, Yanshuo Chu, Ansam Sinjab, Fuduan Peng, Xinmiao Yan, Guangchun Han, Ruiping Wang, Enyu Dai, Yibo Dai, Bogdan A Czerniak, Andrew Futreal, Anirban Maitra, Alexander Lazar, Humam Kadara, Amir A Jazaeri, Xiangdong Cheng, Jaffer Ajani, Jianjun Gao, Jian Hu, Linghua Wang

Student and Faculty Publications

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance …

The Icf Syndrome Protein Cdca7 Harbors A Unique Dna Binding Domain That Recognizes A Cpg Dyad In The Context Of A Non-B Dna, Swanand Hardikar, Ren Ren, Zhengzhou Ying, Jujun Zhou, John R Horton, Matthew D Bramble, Bin Liu, Yue Lu, Bigang Liu, Luis Della Coletta, Jianjun Shen, Jiameng Dan, Xing Zhang, Xiaodong Cheng, Taiping Chen

Student and Faculty Publications

CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Student and Faculty Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

Results Of A Prospective Trial To Evaluate Novel Lung Function Imaging For Lung Cancer Surgery, Lydia J. Wilson, Phd, Richard Castillo, Phd, Edward Castillo, Phd, Bernard Jones, Phd, Moyed Miften, Phd, Lindsey Olsen, Phd, Vikas Aragam, Phd, Robert A. Meguid, Md, Mph, Crystal J. Erickson, Md, Amanda Young, Msn, Matthew Blum, Md, Tyler Grenda, Md, Julie Barta, Md, Benjamin Leiby, Phd, Timothy Waxweiler, Md, Brian Kavanagh, Md, Mph, John D. Mitchell, Md, Yevgeniy Vinogradskiy, Phd

Department of Radiation Oncology Posters

Background

• Surgery is the primary form of definitive treatment for early-stage lung cancer.
• Poor lung function before surgery places patients at high risk of pulmonary complications after resection.
• Surgeons evaluate patient fitness for surgery using pulmonary function tests (PFTs) to calculate the predicted postoperative PFT (ppoPFT).
• Conventional ppoPFT calculations assume homogeneous lung function, which can be inaccurate.
• 4DCT-ventilation is a novel lung function imaging modality developed in radiation oncology that uses 4DCT data to calculate high-resolution ventilation maps.

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Monitoring Response To Neoadjuvant Chemotherapy In Triple Negative Breast Cancer Using Circulating Tumor Dna, Jennifer H Chen, Sridevi Addanki, Dhruvajyoti Roy, Roland Bassett, Ekaterina Kalashnikova, Erik Spickard, Henry M Kuerer, Salyna Meas, Vanessa N Sarli, Anil Korkut, Jason B White, Gaiane M Rauch, Debu Tripathy, Banu K Arun, Carlos H Barcenas, Clinton Yam, Himanshu Sethi, Angel A Rodriguez, Minetta C Liu, Stacy L Moulder, Anthony Lucci

Student and Faculty Publications

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).

METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (Signatera

RESULTS: In total, 37 patients were enrolled. The mean age was 50 …