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Oncology

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Articles 4291 - 4320 of 14295

Full-Text Articles in Medical Specialties

Focal Adhesion Kinase-Yap Signaling Axis Drives Drug-Tolerant Persister Cells And Residual Disease In Lung Cancer, Franziska Haderk, Yu-Ting Chou, Lauren Cech, Celia Fernández-Méndez, Johnny Yu, Victor Olivas, Ismail M Meraz, Dora Barbosa Rabago, D Lucas Kerr, Carlos Gomez, David V Allegakoen, Juan Guan, Khyati N Shah, Kari A Herrington, Oghenekevwe M Gbenedio, Shigeki Nanjo, Mourad Majidi, Whitney Tamaki, Yashar K Pourmoghadam, Julia K Rotow, Caroline E Mccoach, Jonathan W Riess, J Silvio Gutkind, Tracy T Tang, Leonard Post, Bo Huang, Pilar Santisteban, Hani Goodarzi, Sourav Bandyopadhyay, Calvin J Kuo, Jeroen P Roose, Wei Wu, Collin M Blakely, Jack A Roth, Trever G Bivona May 2024

Focal Adhesion Kinase-Yap Signaling Axis Drives Drug-Tolerant Persister Cells And Residual Disease In Lung Cancer, Franziska Haderk, Yu-Ting Chou, Lauren Cech, Celia Fernández-Méndez, Johnny Yu, Victor Olivas, Ismail M Meraz, Dora Barbosa Rabago, D Lucas Kerr, Carlos Gomez, David V Allegakoen, Juan Guan, Khyati N Shah, Kari A Herrington, Oghenekevwe M Gbenedio, Shigeki Nanjo, Mourad Majidi, Whitney Tamaki, Yashar K Pourmoghadam, Julia K Rotow, Caroline E Mccoach, Jonathan W Riess, J Silvio Gutkind, Tracy T Tang, Leonard Post, Bo Huang, Pilar Santisteban, Hani Goodarzi, Sourav Bandyopadhyay, Calvin J Kuo, Jeroen P Roose, Wei Wu, Collin M Blakely, Jack A Roth, Trever G Bivona

Faculty, Staff and Student Publications

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling …


Treatment Outcomes In Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid And/Or Rhabdoid Dedifferentiation After Progression On Immune Checkpoint Therapy, Andrew W Hahn, Devaki Shilpa Surasi, Paul V Viscuse, Tharakeswara K Bathala, Andrew J Wiele, Matthew T Campbell, Amado J Zurita, Amishi Y Shah, Eric Jonasch, Jianjun Gao, Sangeeta Goswami, Omar Alhalabi, Priya Rao, Kanishka Sircar, Nizar M Tannir, Pavlos Msaouel May 2024

Treatment Outcomes In Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid And/Or Rhabdoid Dedifferentiation After Progression On Immune Checkpoint Therapy, Andrew W Hahn, Devaki Shilpa Surasi, Paul V Viscuse, Tharakeswara K Bathala, Andrew J Wiele, Matthew T Campbell, Amado J Zurita, Amishi Y Shah, Eric Jonasch, Jianjun Gao, Sangeeta Goswami, Omar Alhalabi, Priya Rao, Kanishka Sircar, Nizar M Tannir, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated.

PATIENTS AND METHODS: Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for …


Triggering Receptor Expressed On Myeloid Cells 2 (Trem2) Regulates Phagocytosis In Glioblastoma, Mekenzie M Peshoff, Pravesh Gupta, Shivangi Oberai, Rakesh Trivedi, Hiroshi Katayama, Prashanth Chakrapani, Minghao Dang, Simona Migliozzi, Joy Gumin, Divya B Kadri, Jessica K Lin, Nancy K Milam, Mark E Maynard, Brian D Vaillant, Brittany Parker-Kerrigan, Frederick F Lang, Jason T Huse, Antonio Iavarone, Linghua Wang, Karen Clise-Dwyer, Krishna P Bhat May 2024

Triggering Receptor Expressed On Myeloid Cells 2 (Trem2) Regulates Phagocytosis In Glioblastoma, Mekenzie M Peshoff, Pravesh Gupta, Shivangi Oberai, Rakesh Trivedi, Hiroshi Katayama, Prashanth Chakrapani, Minghao Dang, Simona Migliozzi, Joy Gumin, Divya B Kadri, Jessica K Lin, Nancy K Milam, Mark E Maynard, Brian D Vaillant, Brittany Parker-Kerrigan, Frederick F Lang, Jason T Huse, Antonio Iavarone, Linghua Wang, Karen Clise-Dwyer, Krishna P Bhat

Faculty, Staff and Student Publications

Background: Glioblastomas (GBMs) are central nervous system tumors that resist standard-of-care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable antitumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2) is a myeloid signaling regulator that has been implicated in a variety of cancers and neurological diseases with contrasting functions, but its role in GBM immunopathology and progression is still under investigation.

Methods: Our reverse translational investigations leveraged single-cell RNA sequencing and cytometry of human gliomas to characterize TREM2 expression across …


A Comprehensive Approach To Evaluate Genetic Abnormalities In Multiple Myeloma Using Optical Genome Mapping, Ying S Zou, Melanie Klausner, Jen Ghabrial, Victoria Stinnett, Patty Long, Laura Morsberger, Jaclyn B Murry, Katie Beierl, Christopher D Gocke, Rena R Xian, Kevin H Toomer, Jing Christine Ye, Robert Z Orlowski, Carol Ann Huff, Syed Abbas Ali, Philip H Imus, Christian B Gocke, Guilin Tang May 2024

A Comprehensive Approach To Evaluate Genetic Abnormalities In Multiple Myeloma Using Optical Genome Mapping, Ying S Zou, Melanie Klausner, Jen Ghabrial, Victoria Stinnett, Patty Long, Laura Morsberger, Jaclyn B Murry, Katie Beierl, Christopher D Gocke, Rena R Xian, Kevin H Toomer, Jing Christine Ye, Robert Z Orlowski, Carol Ann Huff, Syed Abbas Ali, Philip H Imus, Christian B Gocke, Guilin Tang

Faculty, Staff and Student Publications

No abstract provided.


Evaluating The Heterogeneity Of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis Of Nrg Cc001, Hua-Ren R Cherng, Kai Sun, Søren Bentzen, Terri S Armstrong, Vinai Gondi, Paul D Brown, Minesh Mehta, Mark V Mishra May 2024

Evaluating The Heterogeneity Of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis Of Nrg Cc001, Hua-Ren R Cherng, Kai Sun, Søren Bentzen, Terri S Armstrong, Vinai Gondi, Paul D Brown, Minesh Mehta, Mark V Mishra

Faculty, Staff and Student Publications

Background: Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.

Methods: An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup …


An Unexpected Finding During A Breast Excisional Biopsy: A Case Report, Emily Forester, Anjeanette Brown May 2024

An Unexpected Finding During A Breast Excisional Biopsy: A Case Report, Emily Forester, Anjeanette Brown

Rowan-Virtua Research Day

Background: Pacemaker leads within the breast are rare. Although it is infrequent, there are some reports of implanted cardiac devices or wires migrating into breast tissue or through the chest wall. To the best of our knowledge, there are no current reports of pacemaker leads within the breast tissue of a patient with concurrent breast cancer. This case aims to detail the surgical management of this rare phenomenon.

Case Presentation: A pacemaker-dependent, female patient presented to the operating room for a left breast excisional biopsy. Intraoperatively, two epicardial leads were unexpectedly found within the center of the patient’s breast tissue. …


Resection And Reconstruction Of Ewing Sarcoma Of The Cuboid Utilizing Vascularized Fibular Autograft: A Case Report, Brandon Cunha, Alexandre Arkader May 2024

Resection And Reconstruction Of Ewing Sarcoma Of The Cuboid Utilizing Vascularized Fibular Autograft: A Case Report, Brandon Cunha, Alexandre Arkader

Rowan-Virtua Research Day

Ewing Sarcoma (EWS) rarely presents in the bones of the foot, and particularly in the cuboid, making it an exceedingly rare occurrence. We present the case of a 7-year-old female diagnosed with EWS of the right cuboid, detailing the management and outcomes of this rare presentation. The patient, now almost 5 years post-initial local control, exhibits restored foot function, a normalized gait, and no evidence of disease recurrence. This case underscores the potential for preserving lower extremity function and improving postoperative quality of life in rare presentations of EWS through innovative reconstruction strategies.


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 May 2024

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 May 2024

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 …


Cost-Effectiveness And Outcomes Of Utilizing Tisagenlecleucel Therapy (Car T-Cell) In Pediatric Acute Lymphoblastic Leukemia In Comparison To Standard Of Care (Soc) Therapies: A Scoping Review, Andrew Atschinow, Evangeline Attota, Warren Chan, Pooja Kasarapu, Priyal Shah, Karina Vizzoni May 2024

Cost-Effectiveness And Outcomes Of Utilizing Tisagenlecleucel Therapy (Car T-Cell) In Pediatric Acute Lymphoblastic Leukemia In Comparison To Standard Of Care (Soc) Therapies: A Scoping Review, Andrew Atschinow, Evangeline Attota, Warren Chan, Pooja Kasarapu, Priyal Shah, Karina Vizzoni

Rowan-Virtua Research Day

Aims

This review aims to assess the correlations between outcomes and cost of treatment methods for pediatric acute lymphoblastic leukemia patients, specifically comparing CAR T-cell therapy and Standard-of-Care (SoC) therapy. The socioeconomic background of patients will also be taken into consideration to see if there are differences in their outcomes.

Methods

Peer-reviewed publications were collected from PubMed and Web of Science. The keyword strings used were “acute lymphoblastic leukemia,” “pediatric acute lymphoblastic leukemia,” “pediatric,” “CAR T-cell therapy,” and “cost-effectiveness.” 27 citations were obtained. Titles were screened by 6 authors. Articles met the inclusion criteria including potential Quality-Adjusted Life Year (QALY) …


Physical Medicine & Rehabilitation Referrals In Cancer Patients, Bhumik Patel, Venkateswar Venkataraman, Deanna Janora, Jack Goldberg May 2024

Physical Medicine & Rehabilitation Referrals In Cancer Patients, Bhumik Patel, Venkateswar Venkataraman, Deanna Janora, Jack Goldberg

Rowan-Virtua Research Day

Physical Medicine and Rehabilitation (PM&R) can address functional limitations in various conditions, including cancer. Cancer rehabilitation aims to address functional impairments resulting from both the disease itself and its treatments, striving to optimize physical, social, psychological, and vocational functioning. Existing literature indicates that PM&R services significantly benefit cancer patients by improving their overall quality of life. Studies have found that optimal utilization of PM&R services can increase the Functional Independence Measure (FIM) in cancer patients. Current National Comprehensive Cancer Network and American Cancer Society guidelines emphasize the importance of incorporating PM&R services into oncology care to enhance the function and …


Waiting For A Cure: Factors Influencing Melanoma Treatment Delays, Lisa Huang, David Rubin, Lothar Vidal, Jordan Riser, Christopher Jones, Samantha Hiester May 2024

Waiting For A Cure: Factors Influencing Melanoma Treatment Delays, Lisa Huang, David Rubin, Lothar Vidal, Jordan Riser, Christopher Jones, Samantha Hiester

Rowan-Virtua Research Day

Melanoma, with a five-year survival rate of 94% in early-stage diagnosis, drops significantly when diagnosed at later stages, making identifying barriers to timely treatment crucial. This literature review examines factors influencing melanoma treatment wait times and their impact on patient outcomes. Elderly, male, and Medicare patients, along with those with higher Breslow thickness and severe melanoma stages, experienced longer wait times. Patients receiving intervention within 30 days had better survival rates. Lack of knowledge and misconceptions about melanoma contribute to delayed care, particularly in communities with lower incidence rates. Black patients faced longer waits from diagnosis to surgery, indicating disparities. …


Sunscreen Cost And Its Effect On Skin Cancer In Low-Income Communities: A Systemic Review, John Sauer May 2024

Sunscreen Cost And Its Effect On Skin Cancer In Low-Income Communities: A Systemic Review, John Sauer

Rowan-Virtua Research Day

This research examines the pivotal connection between sunscreen affordability and its impact on skin cancer prevalence, especially in low-income communities. Despite universal dermatological recommendations for daily sunscreen use, stringent criteria contribute to elevated prices, averaging around $10 for a 6 oz unit. This financial strain is compounded for families adhering to recommended application rates, leading to significant economic burdens. Outdoor laborers, less likely to follow guidelines, face heightened risks. Government programs' excluding sunscreen costs further exacerbate challenges for low-income communities, contributing to increased skin cancer incidence. This review aims to establish a correlation between sunscreen cost and skin cancer rates, …


Utilizing Microwave Ablation In Combination With Vertebroplasty Is An Effective Method In Reducing Cancer Related Back Pain, Disability, And Opioid Use: A Systematic Review And Meta-Analysis, Jonathan Elias, Lothar Vidal, Richard Jermyn May 2024

Utilizing Microwave Ablation In Combination With Vertebroplasty Is An Effective Method In Reducing Cancer Related Back Pain, Disability, And Opioid Use: A Systematic Review And Meta-Analysis, Jonathan Elias, Lothar Vidal, Richard Jermyn

Rowan-Virtua Research Day

Background: It is estimated that metastases from primary malignant neoplasms affect the spine around 30%-70% of the time. Many times, these osteolytic tumors will cause the degradation of the vertebrae, leaving patients in a tremendous amount of pain, disability, and dependence on opioids as analgesics. Microwave ablation (MWA) followed by vertebroplasties (VP) has been a developing treatment for such a condition; however, there are no systematic reviews or meta-analyses examining the method’s effectiveness thus far.

Purpose: This systematic review and meta-analysis analyzes the 4-week and 12-week outcomes of patients with metastatic spinal cancer treated with the combinatorial treatment …


Comparative Analysis Of Health Outcomes In Gastric Cancer: Robotic Vs. Laparoscopic Gastrectomy, Maftuna Kurbonnazarova May 2024

Comparative Analysis Of Health Outcomes In Gastric Cancer: Robotic Vs. Laparoscopic Gastrectomy, Maftuna Kurbonnazarova

Rowan-Virtua Research Day

Exploring the most effective surgical approach for gastrectomy is crucial for determining superior health outcomes in patients. This research compares robotic and laparoscopic techniques with the aim of pinpointing the optimal method, offering valuable insights for improved postoperative well-being.


A Rare Presentation: Intracranial Hemorrhage As A Symptom Of Acute Leukemic Transformation In A 23-Year Old Male, Kelsey M. Murray, Kishan B. Patel May 2024

A Rare Presentation: Intracranial Hemorrhage As A Symptom Of Acute Leukemic Transformation In A 23-Year Old Male, Kelsey M. Murray, Kishan B. Patel

Rowan-Virtua Research Day

This case highlights the urgency of considering acute leukemic transformation in young patients presenting with neurological deficits, emphasizing the importance of prompt evaluation and management to optimize patient outcomes. The case depicted is a tragic complication of Chronic Myeloid Leukemia (CML) and its acute blast crisis. Remarkably, the patient exhibited none of the typical constitutional symptoms associated with CML.


Neoadjuvant Versus Adjuvant Therapy For Stage Iiib-Iiid Melanoma, Bhumik Patel, Sangnya Upadhyaya May 2024

Neoadjuvant Versus Adjuvant Therapy For Stage Iiib-Iiid Melanoma, Bhumik Patel, Sangnya Upadhyaya

Rowan-Virtua Research Day

The treatment landscape for advanced stage melanoma is rapidly evolving due to advancements in our understanding of melanoma biology and the emergence of novel therapies. This necessitates a comprehensive review to guide clinicians in adopting evidence based and patient centric approaches to treat stage IIIB-IIID melanoma. A literature review was conducted to synthesize current information on the most optimal treatment available. Data available from different clinical trials found that neoadjuvant therapy was a more effective treatment compared to adjuvant therapies alone. Furthermore, neoadjuvant therapy with combination therapy was more efficacious in producing a complete pathological response compared to monotherapy. A …


Using Genome And Transcriptome Data From African-Ancestry Female Participants To Identify Putative Breast Cancer Susceptibility Genes, Jie Ping, Guochong Jia, Qiuyin Cai, Xingyi Guo, Ran Tao, Christine Ambrosone, Dezheng Huo, Stefan Ambs, Mollie E Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Esther M John, Christopher I Li, Katherine Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Michael F Press, Maureen Sanderson, Dale P Sandler, Toshio Yoshimatsu, Prisca O Adejumo, Thomas Ahearn, Abenaa M Brewster, Anselm J M Hennis, Timothy Makumbi, Paul Ndom, Katie M O'Brien, Andrew F Olshan, Mojisola M Oluwasanu, Sonya Reid, Song Yao, Ebonee N Butler, Maosheng Huang, Atara Ntekim, Bingshan Li, Melissa A Troester, Julie R Palmer, Christopher A Haiman, Jirong Long, Wei Zheng May 2024

Using Genome And Transcriptome Data From African-Ancestry Female Participants To Identify Putative Breast Cancer Susceptibility Genes, Jie Ping, Guochong Jia, Qiuyin Cai, Xingyi Guo, Ran Tao, Christine Ambrosone, Dezheng Huo, Stefan Ambs, Mollie E Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Esther M John, Christopher I Li, Katherine Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Michael F Press, Maureen Sanderson, Dale P Sandler, Toshio Yoshimatsu, Prisca O Adejumo, Thomas Ahearn, Abenaa M Brewster, Anselm J M Hennis, Timothy Makumbi, Paul Ndom, Katie M O'Brien, Andrew F Olshan, Mojisola M Oluwasanu, Sonya Reid, Song Yao, Ebonee N Butler, Maosheng Huang, Atara Ntekim, Bingshan Li, Melissa A Troester, Julie R Palmer, Christopher A Haiman, Jirong Long, Wei Zheng

Faculty, Staff and Student Publications

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.


Kras G12c Inhibitor Combination Therapies: Current Evidence And Challenge, Hirotaka Miyashita, Shumei Kato, David S Hong May 2024

Kras G12c Inhibitor Combination Therapies: Current Evidence And Challenge, Hirotaka Miyashita, Shumei Kato, David S Hong

Faculty, Staff and Student Publications

Although KRAS G12C inhibitors have proven that KRAS is a "druggable" target of cancer, KRAS G12C inhibitor monotherapies have demonstrated limited clinical efficacy due to primary and acquired resistance mechanisms. Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer. Many clinical trials of combinations of KRAS G12C inhibitors with other targeted therapies, such as SOS1, ERK, CDK4/6, and wild-type RAS, are ongoing. Furthermore, preclinical …


Tsyn-Seq: A T-Cell Synapse-Based Antigen Identification Platform, Yimei Jin, Takahiko Miyama, Alexandria Brown, Tomo Hayase, Xingzhi Song, Anand K Singh, Licai Huang, Ivonne I Flores, Lauren K Mcdaniel, Israel Glover, Taylor M Halsey, Rishika Prasad, Valerie Chapa, Saira Ahmed, Jianhua Zhang, Kunal Rai, Christine B Peterson, Gregory Lizee, Jennifer Karmouch, Eiko Hayase, Jeffrey J Molldrem, Chia-Chi Chang, Wen-Bin Tsai, Robert R Jenq May 2024

Tsyn-Seq: A T-Cell Synapse-Based Antigen Identification Platform, Yimei Jin, Takahiko Miyama, Alexandria Brown, Tomo Hayase, Xingzhi Song, Anand K Singh, Licai Huang, Ivonne I Flores, Lauren K Mcdaniel, Israel Glover, Taylor M Halsey, Rishika Prasad, Valerie Chapa, Saira Ahmed, Jianhua Zhang, Kunal Rai, Christine B Peterson, Gregory Lizee, Jennifer Karmouch, Eiko Hayase, Jeffrey J Molldrem, Chia-Chi Chang, Wen-Bin Tsai, Robert R Jenq

Faculty, Staff and Student Publications

Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen …


Fam86a Methylation Of Eef2 Links Mrna Translation Elongation To Tumorigenesis, Joel William Francis, Simone Hausmann, Sabeen Ikram, Kunlun Yin, Robert Mealey-Farr, Natasha Mahealani Flores, Annie Truc Trinh, Tourkian Chasan, Julia Thompson, Pawel Karol Mazur, Or Gozani May 2024

Fam86a Methylation Of Eef2 Links Mrna Translation Elongation To Tumorigenesis, Joel William Francis, Simone Hausmann, Sabeen Ikram, Kunlun Yin, Robert Mealey-Farr, Natasha Mahealani Flores, Annie Truc Trinh, Tourkian Chasan, Julia Thompson, Pawel Karol Mazur, Or Gozani

Faculty, Staff and Student Publications

eEF2 post-translational modifications (PTMs) can profoundly affect mRNA translation dynamics. However, the physiologic function of eEF2K525 trimethylation (eEF2K525me3), a PTM catalyzed by the enzyme FAM86A, is unknown. Here, we find that FAM86A methylation of eEF2 regulates nascent elongation to promote protein synthesis and lung adenocarcinoma (LUAD) pathogenesis. The principal physiologic substrate of FAM86A is eEF2, with K525me3 modeled to facilitate productive eEF2-ribosome engagement during translocation. FAM86A depletion in LUAD cells causes 80S monosome accumulation and mRNA translation inhibition. FAM86A is overexpressed in LUAD and eEF2K525me3 levels increase through advancing LUAD disease stages. FAM86A knockdown attenuates LUAD cell proliferation and suppression …


Community-Acquired Pneumonia: A Us Perspective On The Guideline Gap, Maricar Malinis, Lilian Abbo, Jose A Vazquez, Luis Ostrosky-Zeichner May 2024

Community-Acquired Pneumonia: A Us Perspective On The Guideline Gap, Maricar Malinis, Lilian Abbo, Jose A Vazquez, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.


Mdm2 Inhibitors For Cancer Therapy: The Past, Present, And Future, Wei Wang, Najah Albadari, Yi Du, Josef F Fowler, Hannah T Sang, Wa Xian, Frank Mckeon, Wei Li, Jia Zhou, Ruiwen Zhang May 2024

Mdm2 Inhibitors For Cancer Therapy: The Past, Present, And Future, Wei Wang, Najah Albadari, Yi Du, Josef F Fowler, Hannah T Sang, Wa Xian, Frank Mckeon, Wei Li, Jia Zhou, Ruiwen Zhang

Faculty, Staff and Student Publications

Since its discovery over 35 years ago, MDM2 has emerged as an attractive target for the development of cancer therapy. MDM2's activities extend from carcinogenesis to immunity to the response to various cancer therapies. Since the report of the first MDM2 inhibitor more than 30 years ago, various approaches to inhibit MDM2 have been attempted, with hundreds of small-molecule inhibitors evaluated in preclinical studies and numerous molecules tested in clinical trials. Although many MDM2 inhibitors and degraders have been evaluated in clinical trials, there is currently no Food and Drug Administration (FDA)-approved MDM2 inhibitor on the market. Nevertheless, there are …


Response Of Treatment-Naive Brain Metastases To Stereotactic Radiosurgery, Chibawanye I Ene, Christina Abi Faraj, Thomas H Beckham, Jeffrey S Weinberg, Clark R Andersen, Ali S Haider, Ganesh Rao, Sherise D Ferguson, Christopher A Alvarez-Brenkenridge, Betty Y S Kim, Amy B Heimberger, Ian E Mccutcheon, Sujit S Prabhu, Chenyang Michael Wang, Amol J Ghia, Susan L Mcgovern, Caroline Chung, Mary Frances Mcaleer, Martin C Tom, Subha Perni, Todd A Swanson, Debra N Yeboa, Tina M Briere, Jason T Huse, Gregory N Fuller, Frederick F Lang, Jing Li, Dima Suki, Raymond E Sawaya May 2024

Response Of Treatment-Naive Brain Metastases To Stereotactic Radiosurgery, Chibawanye I Ene, Christina Abi Faraj, Thomas H Beckham, Jeffrey S Weinberg, Clark R Andersen, Ali S Haider, Ganesh Rao, Sherise D Ferguson, Christopher A Alvarez-Brenkenridge, Betty Y S Kim, Amy B Heimberger, Ian E Mccutcheon, Sujit S Prabhu, Chenyang Michael Wang, Amol J Ghia, Susan L Mcgovern, Caroline Chung, Mary Frances Mcaleer, Martin C Tom, Subha Perni, Todd A Swanson, Debra N Yeboa, Tina M Briere, Jason T Huse, Gregory N Fuller, Frederick F Lang, Jing Li, Dima Suki, Raymond E Sawaya

Faculty, Staff and Student Publications

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) …


Sdrnas Participate In The Maintenance And Onset Of Prostate Cancer, Neil Chaudhary May 2024

Sdrnas Participate In The Maintenance And Onset Of Prostate Cancer, Neil Chaudhary

Poster Presentations

What is an sdRNA? Noncoding RNA (ncRNA) is a class of RNA that includes microRNA (miRNA) and small nucleolar RNA (snoRNA). Fragments excised from ncRNAs are known as noncodingderived RNA (ndRNA). A certain class of ndRNAs that are derived from snoRNAs have been denoted as Small Nucleolar Derived RNAs (sdRNAs). Our lab has previously hypothesized and demonstrated that sdRNAs display regulatory functions on target genes, similar to the functions of miRNAs. sdRNAs are almost identical to microRNAs and differ mainly in their source of origin.

Our lab has shown that sdRNA-93 is frequently misexpressed in breast cancer cell lines and …


An Interpretable Framework To Identify Responsive Subgroups From Clinical Trials Regarding Treatment Effects: Application To Treatment Of Intracerebral Hemorrhage, Yaobin Ling, Muhammad Bilal Tariq, Kaichen Tang, Jaroslaw Aronowski, Yang Fann, Sean I Savitz, Xiaoqian Jiang, Yejin Kim May 2024

An Interpretable Framework To Identify Responsive Subgroups From Clinical Trials Regarding Treatment Effects: Application To Treatment Of Intracerebral Hemorrhage, Yaobin Ling, Muhammad Bilal Tariq, Kaichen Tang, Jaroslaw Aronowski, Yang Fann, Sean I Savitz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Randomized Clinical trials (RCT) suffer from a high failure rate which could be caused by heterogeneous responses to treatment. Despite many models being developed to estimate heterogeneous treatment effects (HTE), there remains a lack of interpretable methods to identify responsive subgroups. This work aims to develop a framework to identify subgroups based on treatment effects that prioritize model interpretability. The proposed framework leverages an ensemble uplift tree method to generate descriptive decision rules that separate samples given estimated responses to the treatment. Subsequently, we select a complementary set of these decision rules and rank them using a sparse linear model. …


Optimization, Characterization, And Comparison Of Two Luciferase-Expressing Mouse Glioblastoma Models, Louis Rodgers, Julia A. Schulz Pauly, Bryan J. Maloney, Anika M. S. Hartz, Bjoern Bauer May 2024

Optimization, Characterization, And Comparison Of Two Luciferase-Expressing Mouse Glioblastoma Models, Louis Rodgers, Julia A. Schulz Pauly, Bryan J. Maloney, Anika M. S. Hartz, Bjoern Bauer

UK CARES Faculty Publications

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and the treatment response are typically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences …


Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley May 2024

Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley

Dissertations and Theses (Open Access)

The Monte Carlo particle simulator TOPAS, the multiphysics solver COMSOL., and

several analytical radiation transport methods were employed to perform an in-depth proof-ofconcept

for a high dose rate, high precision converging beam small animal irradiation platform.

In the first aim of this work, a novel carbon nanotube-based compact X-ray tube optimized for

high output and high directionality was designed and characterized. In the second aim, an

optimization algorithm was developed to customize a collimator geometry for this unique Xray

source to simultaneously maximize the irradiator’s intensity and precision. Then, a full

converging beam irradiator apparatus was fit with a multitude …


Fractionated Radiosurgery Associated With High Rates Of Local Control For Large Volume Intact Brain Metastases, Ryan Ko, Hong Ye, Peter Chen, Zachary Seymour, Kuei Lee, Inga Grills May 2024

Fractionated Radiosurgery Associated With High Rates Of Local Control For Large Volume Intact Brain Metastases, Ryan Ko, Hong Ye, Peter Chen, Zachary Seymour, Kuei Lee, Inga Grills

Posters

Radiosurgery is a well-established treatment modality for patients with intact brain metastases, and there is a known impact of tumor size and volume on tumor control. Utilizing our single-institution database, we investigated outcomes for patients with intact brain metastases treated with FSR using LINAC or GK modalities.


Age At Lung Cancer Diagnosis In Females Versus Males Who Never Smoke By Race And Ethnicity, Batel Blechter, Jason Y Y Wong, Li-Hsin Chien, Kouya Shiraishi, Xiao-Ou Shu, Qiuyin Cai, Wei Zheng, Bu-Tian Ji, Wei Hu, Mohammad L Rahman, Hsin-Fang Jiang, Fang-Yu Tsai, Wen-Yi Huang, Yu-Tang Gao, Xijing Han, Mark D Steinwandel, Gong Yang, Yihe G Daida, Su-Ying Liang, Scarlett L Gomez, Mindy C Derouen, W Ryan Diver, Ananya G Reddy, Alpa V Patel, Loïc Le Marchand, Christopher Haiman, Takashi Kohno, Iona Cheng, I-Shou Chang, Chao Agnes Hsiung, Nathaniel Rothman, Qing Lan May 2024

Age At Lung Cancer Diagnosis In Females Versus Males Who Never Smoke By Race And Ethnicity, Batel Blechter, Jason Y Y Wong, Li-Hsin Chien, Kouya Shiraishi, Xiao-Ou Shu, Qiuyin Cai, Wei Zheng, Bu-Tian Ji, Wei Hu, Mohammad L Rahman, Hsin-Fang Jiang, Fang-Yu Tsai, Wen-Yi Huang, Yu-Tang Gao, Xijing Han, Mark D Steinwandel, Gong Yang, Yihe G Daida, Su-Ying Liang, Scarlett L Gomez, Mindy C Derouen, W Ryan Diver, Ananya G Reddy, Alpa V Patel, Loïc Le Marchand, Christopher Haiman, Takashi Kohno, Iona Cheng, I-Shou Chang, Chao Agnes Hsiung, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke.

METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes.

RESULTS: We found that among Chinese individuals diagnosed with lung cancer …