Neoplasms Commons^™

Efficacy Of Mcl-1 Inhibitors In Multiple Myeloma Cells Resistant To Bortezomib, Emily Nelson, Omar S. Al-Odat, Sabrina M. Paparo, Daniel A. Guirguis, Gabriella Yao, Manoj Pandey, Subash Jonnalagadda, Tulin Budak-Alpdogan

Rowan-Virtua Research Day

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, …

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …

Acute Pain Prediction In Oral Cavity And Oropharyngeal Cancer Patients Receiving Radiation Therapy, Vivian Salama

Dissertations and Theses (Open Access)

Oral-Cavity and oropharyngeal cancers (OC/OPC) are types of head and neck cancers that are increasing in incidence domestically. Radiation therapy (RT) is crucial in OC/OPC management. Pain is a common and challenging symptom for most patients during therapy, as nearly all patients undergoing locoregional RT in OC/OPC require analgesia for acute iatrogenic pain. Moreover, about 45% of long-term survivors report chronic pain, with more than 10% exhibiting severe chronic pain. Pain control is challenging due to the multifactorial clinical, molecular, and cellular etiology of cancer/therapy pain, as well as variation in pain assessment and the non-uniform management of pain between …

Jak2v617f Reversible Activation Shows Its Essential Requirement In Myeloproliferative Neoplasms, Andrew J Dunbar, Robert L Bowman, Young C Park, Kavi O'Connor, Franco Izzo, Robert M Myers, Abdul Karzai, Zachary Zaroogian, Won Jun Kim, Inés Fernández-Maestre, Michael R Waarts, Abbas Nazir, Wenbin Xiao, Tamara Codilupi, Max Brodsky, Mirko Farina, Louise Cai, Sheng F Cai, Benjamin Wang, Wenbin An, Julie L Yang, Shoron Mowla, Shira E Eisman, Amritha Varshini Hanasoge Somasundara, Jacob L Glass, Tanmay Mishra, Remie Houston, Emily Guzzardi, Anthony R Martinez Benitez, Aaron D Viny, Richard P Koche, Sara C Meyer, Dan A Landau, Ross L Levine

Faculty, Staff and Student Publications

Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic …

Decorin Suppresses Tumor Lymphangiogenesis: A Mechanism To Curtail Cancer Progression, Dipon K. Mondal, Christopher Xie, Gabriel J. Pascal, Simone Buraschi, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, …

In Silico And In Vitro Study Of Isoquercitrin Against Kidney Cancer And Inflammation By Triggering Potential Gene Targets, Safia Iqbal, Md Rezaul Karim, Shahnawaz Mohammad, Jong Chan Ahn, Anjali Kariyarath Valappil, Ramya Mathiyalagan, Deok-Chun Yang, Dae-Hyo Jung, Hyocheol Bae, Dong Uk Yang

Faculty, Staff and Student Publications

Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto …

First-In-Human Phase I Study Of Tinengotinib (Tt-00420), A Multiple Kinase Inhibitor, As A Single Agent In Patients With Advanced Solid Tumors, Sarina A Piha-Paul, Binghe Xu, Ecaterina E Dumbrava, Siqing Fu, Daniel D Karp, Funda Meric-Bernstam, David S Hong, Jordi A Rodon, Apostolia M Tsimberidou, Kanwal Raghav, Jaffer A Ajani, Anthony P Conley, Frank Mott, Ying Fan, Jean Fan, Peng Peng, Hui Wang, Shumao Ni, Caixia Sun, Xiaoyan Qiang, Wendy J Levin, Brenda Ngo, Qinhua Cindy Ru, Frank Wu, Milind M Javle

Faculty, Staff and Student Publications

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors.

PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy.

RESULTS: Forty-eight patients were enrolled (dose escalation, …

Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi

Faculty, Staff and Student Publications

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways …

Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity …

Prediction Of Cancer Incidence And Mortality In Korea, 2024, Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo

Faculty, Staff and Student Publications

PURPOSE: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden.

MATERIALS AND METHODS: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which …

Randomized Phase 2 Trial Of Tremelimumab And Durvalumab In Combination Versus Sequentially In Recurrent Platinum-Resistant Ovarian Cancer, Emily M Hinchcliff, Anne Knisely, Naomi Adjei, Bryan Fellman, Ying Yuan, Ami Patel, Cai Xu, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Nicole D Fleming, David M Gershenson, Raghunandan Vikram, Tharakeswara Bathala, David Vining, Dhakshina M Ganeshan, Karen H Lu, Charlotte C Sun, Larissa A Meyer, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end …

Remodeling Anaplastic Thyroid Cancer’S Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite treatment advances, breast cancer remains a leading cause of death of women in the United States, mostly due to metastatic disease. Bone is a preferential site for breast cancer metastasis, and most metastatic breast cancer patients experience bone involvement at the time of death. The majority of patients with bone metastatic breast cancer are first diagnosed with and treated for early-stage disease, and from development of early-stage breast cancer to the recurrence of cancer in the bones, up to 30 years may elapse. Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Trps1 Expression In Non-Melanocytic Cutaneous Neoplasms: An Immunohistochemical Analysis Of 200 Cases, Yi A Liu, Phyu P Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Qingqing Ding, Woo Cheal Cho

Faculty, Staff and Student Publications

BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.

METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Mortality After Major Cardiovascular Events In Survivors Of Childhood Cancer, Wendy Bottinor, Cindy Im, David R Doody, Saro H Armenian, Alexander Arynchyn, Borah Hong, Rebecca M Howell, David R Jacobs, Kirsten K Ness, Kevin C Oeffinger, Alexander P Reiner, Gregory T Armstrong, Yutaka Yasui, Eric J Chow

Faculty, Staff and Student Publications

Background: Adult survivors of childhood cancer are at risk for cardiovascular events.

Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations.

Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical …

Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir

Kimmel Cancer Center Faculty Papers

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural …

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

Reconstitution Of Human Pdac Using Primary Cells Reveals Oncogenic Transcriptomic Features At Tumor Onset, Yi Xu, Michael H Nipper, Angel A Dominguez, Zhenqing Ye, Naoki Akanuma, Kevin Lopez, Janice J Deng, Destiny Arenas, Ava Sanchez, Francis E Sharkey, Colin M Court, Aatur D Singhi, Huamin Wang, Martin E Fernandez-Zapico, Lu-Zhe Sun, Siyuan Zheng, Yidong Chen, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the …

Non-Canonical Hedgehog Signaling Mediates Profibrotic Hematopoiesis-Stroma Crosstalk In Myeloproliferative Neoplasms, Jessica E Pritchard, Juliette E Pearce, Inge A M Snoeren, Stijn N R Fuchs, Katrin Götz, Fabian Peisker, Silke Wagner, Adam Benabid, Niklas Lutterbach, Vanessa Klöker, James S Nagai, Monica T Hannani, Anna K Galyga, Ellen Sistemich, Bella Banjanin, Niclas Flosdorf, Eric Bindels, Kathrin Olschok, Katharina Biaesch, Nicolas Chatain, Neha Bhagwat, Andrew Dunbar, Rita Sarkis, Olaia Naveiras, Marie-Luise Berres, Steffen Koschmieder, Ross L Levine, Ivan G Costa, Hélène F E Gleitz, Rafael Kramann, Rebekka K Schneider

Faculty, Staff and Student Publications

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …

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 …

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 …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …