Medicine and Health Sciences Commons^™

Efficacy Of Full Dose And Sandwich Neoadjuvant Chemotherapy In Breast Cancer: A Literature Review, I Gusti Ng Wibisana, Shandy V. Putra

The New Ropanasuri Journal of Surgery

Introduction. Breast cancer is the leading cause of death in productive-age women, and that needs to be addressed with systemic medication. There has been a big-scale success using adjuvant chemotherapy; however, the optimal method of chemotherapy administration has yet to be determined. Two methods have been introduced today: full dose and sandwich methods. In full dose, we administer chemotherapy before surgical intervention, whereas in the sandwich method, we administer chemotherapy before and after surgical intervention. In this literature review, we aim to observe the effectiveness of chemotherapy administration through both full-dose and sandwich methods.

Method. In the initial phase, 51 …

From Graph Theory For Robust Deep Networks To Graph Learning For Multimodal Cancer Analysis, Asim Waqas

USF Tampa Graduate Theses and Dissertations

This dissertation explores the intersection of graph theory and deep learning, focusing on enhancing the robustness of deep neural networks (DNNs) and applying these advancements to complex problems like cancer diagnosis and treatment. We investigate the structural properties of graphs and their influence on neural network performance, particularly in multimodal learning. The work delves into the design space of DNN architectures using graph-theoretic measures, transforming graphs into DNN architectures for various tasks, and examining their robustness against noise and adversarial attacks. The study extends to medical imaging, highlighting advanced DNN architectures like U-Net for brain tumor segmentation. It addresses the …

Cross-Sectional Analysis Of The Association Between Household Food Insecurity And Mental Health Conditions In Children Aged 5–11 Years In Canada, Justin Thielman, Sarah Orr, Saranya Naraentheraraja, Daniel Harrington, Sarah Carsley

Faculty, Staff and Student Publications

BACKGROUND: Children living in food insecure households have poorer mental health outcomes compared with their food-secure peers; however, the relationship between the severity of food insecurity and diagnosed mental health conditions in young children remains unknown. This study examined the association between household food insecurity and reported diagnosed mental health conditions among children aged 5-11 years in Canada.

METHODS: This study included 16 216 children aged 5-11 years living in Canada, from the 2019 Canadian Health Survey on Children and Youth. We measured household food insecurity using the Household Food Security Survey Module. We measured diagnosed mental health conditions by …

Impact Of Rural Location On Receipt Of Standard Of Care Treatment And Survival For Locally Advanced Bladder Cancer In Louisiana, Megan Escott, Yong Yi, Ashley Foret, Ting Ting Li, Mei Chin Hsieh, Scott E. Delacroix, Xiao Cheng Wu, Mary E. Westerman

School of Public Health Faculty Publications

Objective: We aim to determine the effect of region of residence (urban vs. rural) on the odds of receiving standard of care treatment for locally advanced BCa in Louisiana and its impact on survival outcomes. Methods: Using the Louisiana Tumor Registry, we identified American Joint Committee on Cancer (AJCC) stage II or III, BCa diagnoses in Louisiana residents between 2010 and 2020. Treatment received was classified as standard or non-standard of care according to American Urological Association (AUA) guidelines and location of residence was determined using Rural Urban Commuting Area-Tract-level 2010 (RUCA). Multivariable logistic regression analyses and multivariate cox proportional …

Long-Term Outcomes In Patients Using Protocol-Directed Active Surveillance For Prostate Cancer, Lisa F. Newcomb, Jeannette M. Schenk, Yingye Zheng, Menghan Liu, Kehao Zhu, James D. Brooks, Peter R. Carroll, Atreya Dash, Claire M. De La Calle, William J. Ellis, Christopher P. Filson, Martin E. Gleave, Michael A. Liss, Frances Martin, Jesse K. Mckenney, Todd M. Morgan, Maria S. Tretiakova, Andrew A. Wagner, Peter S. Nelson, Daniel W. Lin

Markey Cancer Center Faculty Publications

IMPORTANCE: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making.

OBJECTIVE: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort.

DESIGN, SETTING, AND PARTICIPANTS: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008. A cohort of 2155 men with favorable-risk prostate cancer and no prior treatment were enrolled at 10 North American centers through August 2022.

EXPOSURE: Active surveillance for prostate cancer.

MAIN OUTCOMES AND MEASURES: Cumulative incidence of biopsy grade reclassification, treatment, metastasis, prostate cancer mortality, overall mortality, and recurrence after …

Car T-Cell Expansion: Harmful Or Helpful?, Anath C Lionel, Sattva S Neelapu

Faculty, Staff and Student Publications

No abstract provided.

Hypoxia Inducible Factor 2Α Promotes Tolerogenic Macrophage Development During Cardiac Transplantation Through Transcriptional Regulation Of Colony Stimulating Factor 1 Receptor, Matthew Deberge, Samantha Schroth, Fanfan Du, Xin Yi Yeap, Jiao-Jing Wang, Zheng Jenny Zhang, Mohammed Javeed Ansari, Evan A Scott, Edward B Thorp

Faculty, Staff and Student Publications

Solid organ transplantation mobilizes myeloid cells, including monocytes and macrophages, which are central protagonists of allograft rejection. However, myeloid cells can also be functionally reprogrammed by perioperative costimulatory blockade to promote a state of transplantation tolerance. Transplantation tolerance holds promise to reduce complications from chronic immunosuppression and promote long-term survival in transplant recipients. We sought to identify different mediators of transplantation tolerance by performing single-cell RNA sequencing of acute rejecting or tolerized cardiac allografts. This led to the unbiased identification of the transcription factor, hypoxia inducible factor (HIF)-2α, in a subset of tolerogenic monocytes. Using flow cytometric analyses and mice …

Cracd Loss Induces Neuroendocrine Cell Plasticity Of Lung Adenocarcinoma, Bongjun Kim, Shengzhe Zhang, Yuanjian Huang, Kyung-Pil Ko, Youn-Sang Jung, Jinho Jang, Gengyi Zou, Jie Zhang, Sohee Jun, Kee-Beom Kim, Kwon-Sik Park, Jae-Il Park

Faculty, Staff and Student Publications

Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, some lung adenocarcinoma (LUAD) cells transform into neuroendocrine (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD (capping protein inhibiting regulator of actin dynamics), a capping protein inhibitor, is frequently inactivated in cancers. CRACD knockout (KO) is sufficient to de-repress NE-related gene expression in the pulmonary epithelium and LUAD cells. In LUAD mouse models, Cracd KO increases intratumoral heterogeneity with NE gene expression. Single-cell transcriptomic analysis showed that Cracd KO-induced NE cell plasticity is associated with cell de-differentiation and stemness-related pathway activation. The …

A Spatiotemporal Map Of Co-Receptor Signaling Networks Underlying B Cell Activation, Katherine J Susa, Gary A Bradshaw, Robyn J Eisert, Charlotte M Schilling, Marian Kalocsay, Stephen C Blacklow, Andrew C Kruse

Faculty, Staff and Student Publications

The B cell receptor (BCR) signals together with a multi-component co-receptor complex to initiate B cell activation in response to antigen binding. Here, we take advantage of peroxidase-catalyzed proximity labeling combined with quantitative mass spectrometry to track co-receptor signaling dynamics in Raji cells from 10 s to 2 h after BCR stimulation. This approach enables tracking of 2,814 proximity-labeled proteins and 1,394 phosphosites and provides an unbiased and quantitative molecular map of proteins recruited to the vicinity of CD19, the signaling subunit of the co-receptor complex. We detail the recruitment kinetics of signaling effectors to CD19 and identify previously uncharacterized …

Clinical And Genomic Profile Of Primary Cranial Neurolymphomatosis, Emily B Wolf, Robin Imperial, Liuyan Jiang, Amit K Agarwal, Han W Tun

Faculty, Staff and Student Publications

Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by …

Integration Of Electrospun Scaffolds And Biological Polymers For Enhancing The Delivery And Efficacy Of Mesenchymal Stem/Stromal Cell Therapies, Allan John R Barcena, Archana Mishra, Dominic Karl M Bolinas, Benjamin M Martin, Marites P Melancon

Faculty, Staff and Student Publications

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity …

Black Holes In Time: The Effect Of Grid Radiation On The Tumor Immune Microenvironment, Rebecca A. Bekker

USF Tampa Graduate Theses and Dissertations

Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed ‘hot’ tumor beds, or ‘cold’ immune deserts with low levels of infiltration. The pre-treatment immune state of the TIME is associated with treatment outcome; immunologically hot tumors generally exhibit better responses to radio- and immunotherapy than cold tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation induced tumoricidal immune response is curtailed by subsequent applications of radiation. Thus, I hypothesize that spatially fractionated radiotherapy (SFRT), administered …

Aso Author Reflections: Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma And Operative Margin Revision, Lee M. Ocuin

Faculty Scholarship

No abstract provided.

Multiple Omics Levels Of Chronic Lymphocytic Leukemia, Aleksander Turk, Eva Čeh, George A Calin, Tanja Kunej

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy characterized by the proliferation of functionally mature but incompetent B cells. It is the most prevalent type of leukemia in Western populations, accounting for approximately 25% of new leukemia cases. While recent advances, such as ibrutinib and venetoclax treatment have improved patient outlook, aggressive forms of CLL such as Richter transformation still pose a significant challenge. This discrepancy may be due to the heterogeneity of factors contributing to CLL development at multiple -omics levels. However, information on the omics of CLL is fragmented, hindering multi-omics-based research into potential treatment options. To address …

Elucidating Immune-Related Gene Transcriptional Programs Via Factorization Of Large-Scale Rna-Profiles, Shan He, Matthew M Gubin, Hind Rafei, Rafet Basar, Merve Dede, Xianli Jiang, Qingnan Liang, Yukun Tan, Kunhee Kim, Maura L Gillison, Katayoun Rezvani, Weiyi Peng, Cara Haymaker, Sharia Hernandez, Luisa M Solis, Vakul Mohanty, Ken Chen

Faculty, Staff and Student Publications

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated …

Association Between Obstructive Sleep Apnea And Risk Of Benign Vocal Fold Lesions: A Nationwide 9-Year Follow-Up Cohort Study, Yong Tae Hong, Min Gu Kang, Min Gyu Lee, Sang Woo Yeom, Jong Seung Kim

Faculty, Staff and Student Publications

Since obstructive sleep apnea (OSA) affects various parts of the body, there has been little interest about the effect of OSA on voice. The objective of this study was to evaluate the risk of benign vocal fold lesions (BVFL) in OSA patients. This study used data from the National Health Insurance Service (NHIS) database. The study group was defined as the group diagnosed with OSA between 2008 and 2011. Non-OSA groups were selected based on propensity score (PS) matching. Incidence of BVFL among participants during the follow-up was analyzed. Cox proportional hazard regression analyses were performed to evaluate the association …

Elderly Mice With History Of Acetaminophen Intoxication Display Worsened Cognitive Impairment And Persistent Elevation Of Astrocyte And Microglia Burden, Celso S G Catumbela, Rodrigo Morales

Faculty, Staff and Student Publications

Acetaminophen (APAP) is a leading cause of acute liver failure. The effect of APAP metabolite's effects in the periphery are well characterized; however, associated consequences in the brain remain poorly understood. Animal studies on this subject are few and reveal that frequent APAP intake can trigger cerebral abnormalities that vary depending on the subject's age. Alarmingly, experimental efforts have yet to examine associated consequences in elderly hosts, who correspond to the highest risk of medication overload, impaired drug clearance, and cognitive deficits. Here, we interrogated the cerebral and peripheral pathology of elderly mice submitted to monthly episodes of APAP intoxication …

Erratum: Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

What Are The Lessons Learned From A Survivorship Trial During The Pandemic?, Alanna J. Horowitz, Sharneet J. Sandhu, Sherry J. Guo, Gabriel Barreto-D'Silva, Leonardo Barreto-D'Silva, Krishna Gunturu

The Lahey Journal

Purpose: The American Cancer Society (ACS) has acknowledged the importance of maintaining a healthy diet and engaging in regular physical activity for cancer survivors. While studies have found that adherence to these guidelines improves long-term quality of life, several studies showed that up to 70% of cancer survivors do not meet the standards. The purpose of this pilot study is to determine the effectiveness of a multi-disciplinary survivorship clinic (MDSC) in helping patients adhere to the ACS survivorship guidelines and its impacts on quality of life (QOL).

Methods: Primary objective of the study is to encourage cancer patients to adhere …

Neuroecological Links Of The Exposome And One Health, Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A Eyre

Faculty, Staff and Student Publications

This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required for environmental health strategies. Ibanez et al. address current gaps and strategies needed in research, policy, and technology, offering a road map for stakeholders.

Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo

Faculty, Staff and Student Publications

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor …

Keep Fingers On The Cpg Islands, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

To Revise Or Not Revise? Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma, Victoria S. Wu, Henry J. Stitzel, John B. Ammori, Jeffrey Hardacre, Lee M. Ocuin

Faculty Scholarship

Background: The study determined the proportion of patients with pancreatic adenocarcinoma (PDAC) who had margin-positive disease and no other adverse pathologic findings (APF) using institutional and administrative datasets. Methods: Patients with clinical stage I or II PDAC in the National Cancer Database (NCDB 2010–2020) and those who underwent pancreatectomy at the authors’ institution (2010–2021) were identified. Isolated margin positivity (IMP) was defined as a positive surgical margin with no APF (negative nodes, no lymphovascular/perineural invasion). Results: The study included 225 patients from the authors’ institution and 23,598 patients from the NCDB. The margin-positive rates were 21.8% and 20.3%, and the …

Effects Of Exercise Or Metformin On Myokine Concentrations In Patients With Breast And Colorectal Cancer: A Phase Ii Multi-Centre Factorial Randomized Trial, Justin C. Brown, Guillaume Spielmann, Shengping Yang, Stephanie L.E. Compton, Lee W. Jones, Melinda L. Irwin, Jennifer A. Ligibel, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. Methods: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I–III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were …

The Cdk9 Inhibitor Enitociclib Overcomes Resistance To Btk Inhibition And Car-T Therapy In Mantle Cell Lymphoma, Vivian Jiang, William Lee, Tianci Zhang, Alexa Jordan, Fangfang Yan, Qingsong Cai, Joseph Mcintosh, Jovanny Vargas, Yang Liu, Michael Wang

Faculty, Staff and Student Publications

Inhibitors of Bruton's tyrosine kinase (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 are paradigm-shifting advances in treating patients with aggressive mantle cell lymphoma (MCL). However, clinical relapses following BTKi and CD19-directed CAR-T treatments are a fast-growing medical challenge. Development of novel therapies to overcome BTKi resistance (BTKi-R) and BTKi-CAR-T dual resistance (Dual-R) are urgently needed. Our single-cell RNA sequencing data revealed major transcriptomic reprogramming, with great enrichment of MYC-targets evolving as resistance to these therapies developed. Interestingly, cyclin-dependent kinase 9 (CDK9), a critical component of the positive transcription elongation factor-b complex, was among the top upregulated genes …

Neurogranin Modulates The Rate Of Association Between Calmodulin And Target Peptides, John A Putkey, Laurel Hoffman, Vladimir Berka, Xu Wang

Faculty, Staff and Student Publications

The best-known mode of action of calmodulin (CaM) is binding of Ca2+ to its N- and C-domains, followed by binding to target proteins. An underappreciated facet of this process is that CaM is typically bound to proteins at basal levels of free Ca2+, including the small, intrinsically disordered, neuronal IQ-motif proteins called PEP-19 and neurogranin (Ng). PEP-19 and Ng would not be effective competitive inhibitors of high-affinity Ca2+-dependent CaM targets at equilibrium because they bind to CaM with relatively low affinity, but they could influence the time course of CaM signaling by affecting the rate of association of CaM with …

Targeting Il-11r/Ezh2 Signaling Axis As A Therapeutic Strategy For Osteosarcoma Lung Metastases, Eswaran Devarajan, R Eric Davis, Hannah C Beird, Wei-Lien Wang, V Behrana Jensen, Arumugam Jayakumar, Cheuk Hong Leung, Heather Y Lin, Chia-Chin Wu, Stephanie A Ihezie, Jen-Wei Tsai, P Andrew Futreal, Valerae O Lewis

Faculty, Staff and Student Publications

Lung metastases are the primary cause of death for osteosarcoma (OS) patients. We recently validated interleukin-11 receptor α (IL-11Rα) as a molecular target for the inhibition of OS lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rα signaling. We used shRNA to deplete IL-11Rα from OS cells; as a complementary approach, we added IL-11 exogenously to OS cells. The resulting changes in gene expression identified EZH2 as a downstream candidate. This was confirmed by knockdown of IL-11Rα in OS cells, which led to increased expression …

Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke

Faculty, Staff and Student Publications

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …