Medicine and Health Sciences Commons^™

Nuclear Destabilisation – A Possible Genesis Of Cancer?, Daniel D. Scott, Francesco Bettariga, Marco Ventin, Chris Bishop, Britta Stordal

Research outputs 2022 to 2026

This review examines the increasingly prominent role of mechanics within cancer formation and progression. The extremely varied and contradictory genetic landscape of cancer is in stark contrast to the seemingly universal mechanical characteristics of cancer cells and their tumour microenvironment, and mechanics may be a principal unifying trait of this disease. The tight regulation of innate cell mechanical properties raises the possibility that destabilisation of the cell drives tumour formation in an attempt to restore cell mechanical homeostasis. With losses in cell stiffness more pronounced at the cell nucleus, we hypothesise that destabilisation occurs within the nucleus, likely within the …

Investigating The Role Of Rps3 In The Homologous Recombination Dna Repair Pathway, Jerome Robert Dorsey

Theses and Dissertations

Ribosomal proteins have been demonstrated to perform extra-ribosomal functions beyond protein synthesis, including roles in cell signaling, transcription regulation, apoptosis, and DNA repair. Ribosomal protein S3 (RPS3), in particular, has been implicated in DNA repair and apoptosis pathways, suggesting a critical role in maintaining genomic stability. However, the specific mechanisms involving RPS3 are still unknown, particularly in the context of double-stranded break (DSB) repair. DSBs are among the most severe types of DNA damage, often resulting in chromosomal instability or cell death if not properly repaired. Nonhomologous End Joining (NHEJ) and Homologous Recombination (HR) are the two primary DNA repair …

Prognostic Value Of Neutrophil-To-Lymphocyte Ratio, Platelet-To-Lymphocyte Ratio, And Lactate Dehydrogenase Level In Melanoma Patients Treated With Immune Checkpoint Inhibitors, Wynne Wijaya, Muhammad Adnan Khattak, Afaf Abed, Tarek Meniawy, Michael Millward, Elin Gray, Oliver Oey

Research outputs 2022 to 2026

Introduction: Metastatic melanoma carries a poor prognosis. Immune checkpoint inhibitors (ICIs) have improved outcomes, but responses remain variable, highlighting the need for simple prognostic biomarkers. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) reflect tumour burden and inflammation, though their clinical utility is unstandardised. Methods: We retrospectively analysed 103 metastatic melanoma patients treated with anti-PD-1 monotherapy at two centres in Western Australia (2014–2020). Baseline NLR, PLR, and LDH were assessed within 30 days pre-treatment. Outcomes included clinical benefit, progression-free survival (PFS), and overall survival (OS). Results: Poor ECOG performance status (PS ≥2) (RR 2.39, …

Clinical Impact Of Sub-Clonal Ras/Braf Alterations In Liquid Biopsies From Patients With Advanced Or Metastatic Crc, Peter Gibbs, Khalid Abubaker, Danyi Wang, Zheng Feng, Jawad Hamad, Jiemin Liao, Christopher Stroh, Soetkin Vlassak, Kathrin Heinrich, Adnan Khattak, Juergen Scheuenpflug

Research outputs 2022 to 2026

Introduction: Colorectal cancer (CRC), a global health concern, requires effective treatments. Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are used for RAS wild-type and BRAFV600 mutation-negative metastatic CRC (mCRC) but are not indicated for RAS mutant CRC. Evidence suggests CRC patients with sub-clonal RAS/BRAF mutations in tumor tissue may benefit from anti-EGFRs. We assessed the outcomes of patients with sub-clonal RAS/BRAF mutated advanced/mCRC receiving anti-EGFRs using liquid-based GuardantINFORM real-world clinical-genomic analysis. Patients and Methods: GuardantINFORM analyzed US patients with advanced CRC with BRAFV600/KRAS/NRAS mutations who received anti-EGFR therapies within 90 days after a Guardant360 test. Primary endpoints were time-to-next treatment …

Intake Of Total, Classes, And Subclasses Of (Poly)Phenols And Risk Of Lymphoid Neoplasms: A Prospective Analysis In The Epic Cohort, Enrique Almanza-Aguilera, David Guananga-Álvarez, Yolanda Benavente, Alexandra Nieters, Caroline Besson, Fatemeh Saberi Hosnijeh, Cecilie Kyrø, Nicola P. Bondonno, Christina C. Dahm, Elisabete Weiderpass, Therese Truong, Mariem Louati-Hajji, Xuan Ren, Verena Katzke, Matthias B. Schulze, Fabrizio Pasanisi, Claudia Vener, Giovanna Masala, Maria Teresa Giraudo, Rosario Tumino, Amaia Aizpurua, Maria Jose Sánchez, José María Huerta, Marcela Guevara, Cristina Lasheras, Paolo Vineis

Research outputs 2022 to 2026

Background: Existing epidemiological evidence regarding the potential role of (poly)phenol intake in lymphoma development is limited. Methods: We investigated the associations between the intake of total and individual classes and subclasses of (poly)phenols and the risk of lymphoma, including main frequent subtypes in the EPIC cohort using multivariable-adjusted Cox proportional hazards models. Results: During a mean 14-year follow-up (time frame: from 1990–1994 to 2008–2013), 2394 incident lymphoma cases were diagnosed from a total of 367,463 individuals. No significant associations were observed between total intakes of (poly)phenols, flavonoids, and phenolic acids and overall lymphoma risk. Total (poly)phenols, phenolic acid and hydroxycinnamic …

Neoadjuvant Anti-Pd-1 Alone Or In Combination With Anti-Tigit Or An Oncolytic Virus In Resectable Stage Iiib–D Melanoma: A Phase 1/2 Trial, Reinhard Dummer, Caroline Robert, Richard A. Scolyer, Janis M. Taube, Michael T. Tetzlaff, Alexander M. Menzies, Andrew Hill, Jean Jacques Grob, David C. Portnoy, Celeste Lebbe, Muhammad A. Khattak, Jonathan Cohen, Gil Bar-Sela, Inderjit Mehmi, Ronnie Shapira-Frommer, Nicolas Meyer, Andrea L. Webber, Yixin Ren, Mizuho Fukunaga-Kalabis, Clemens Krepler, Georgina V. Long

Research outputs 2022 to 2026

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB–D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 (47%) patients, …

Nivolumab Plus Chemotherapy Or Ipilimumab In Gastroesophageal Cancer: Exploratory Biomarker Analyses Of A Randomized Phase 3 Trial, Kohei Shitara, Yelena Y. Janjigian, Jaffer Ajani, Markus Moehler, Jin Yao, Xuya Wang, Aparna Chhibber, Dimple Pandya, Lin Shen, Marcelo Garrido, Carlos Gallardo, Lucjan Wyrwicz, Kensei Yamaguchi, Tomasz Skoczylas, Arinilda Bragagnoli, Tianshu Liu, Michael Schenker, Patricio Yañez, Ruben Kowalyszyn, Michalis Karamouzis, Thomas Zander, Kynan Feeney, Elena Elimova, Parul Doshi, Mingshun Li, Ming Lei

Research outputs 2022 to 2026

First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) and progression-free survival versus chemotherapy for advanced gastroesophageal adenocarcinoma with programmed death ligand 1 combined positive score ≥ 5, meeting both primary end points of the randomized phase 3 CheckMate 649 trial. Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, post hoc exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein–Barr virus-positive tumors compared with chromosomally unstable and …

Survival After Cessation Of Immunotherapies In Melanoma: A Systematic Review And Meta-Analysis, Kristine E. Mayer, Lydia Warburton, Anne Zaremba, Sarah Preis, Yannick Foerster, Tilo Biedermann, Oana Diana Persa

Research outputs 2022 to 2026

Background: Immune-checkpoint inhibitor (ICI) therapy elicits durable responses in a subset of patients with advanced melanoma. However, the appropriate timing for treatment cessation remains an unresolved issue. Moreover, some patients are required to discontinue therapy due to the occurrence of severe adverse events. Upon treatment cessation, a subset of patients maintains a durable response, while some patients relapse and require rechallenge with ICI. Criteria for a safe stop of ICI have not been established. Objectives: The aim of this systematic review and meta-analysis was to evaluate the durability of response in melanoma patients who discontinued ICI therapy. Furthermore, the outcome …

Feasibility And Psychometric Quality Of Smartphone Administered Cognitive Ecological Momentary Assessments In Women With Metastatic Breast Cancer, Ashley M. Henneghan, Emily W. Paolillo, Kathleen M. Van Dyk, Oscar Y. Franco-Rocha, Soyeong Bang, Rebecca Tasker, Tara Kaufmann, Darren Haywood, Nicolas H. Hart, Raeanne C. Moore

Research outputs 2022 to 2026

Objective: Metastatic breast cancer (MBC) is associated with burdensome side effects, including cognitive changes that require ongoing monitoring. Cognitive ecological momentary assessments (EMAs) allow for assessment of individual cognitive functioning in natural environments and can be administered via smartphones. Accordingly, we sought to establish the feasibility, reliability, and validity of a commercially available cognitive EMA platform. Methods: Using a prospective design, clinical cognitive and psychosocial assessments (cognitive batteries; patient reported outcomes) were collected at baseline, followed by a 28-day daily EMA protocol that included self-ratings for symptoms and mobile cognitive tests (memory, executive functioning, working memory, processing speed). Satisfaction and …

Proximity To Cancer Rehabilitation And Exercise Oncology By Geography, Race, And Socioeconomic Status, Kathryn H. Schmitz, Kathryn Demanelis, Mary E. Crisafio, Mary A. Kennedy, Anna L. Schwartz, Anna Campbell, Jessica Gorzelitz, Kelley C. Wood, Christopher M. Wilson, Raymond L. Scalise, Alex Vincent

Research outputs 2022 to 2026

Background: Cancer rehabilitation and exercise oncology (CR/EO) have documented benefits for people living with and beyond cancer. The authors examined proximity to CR/EO programs across the United States with respect to population density, race and ethnicity, socioeconomic status, and cancer incidence and mortality rates.

Methods: This cross-sectional study was conducted in 2022–2023. Online searches were initiated to identify CR/EO programs. Geocoding was used to obtain latitudinal and longitudinal geospatial coordinates. Demographic data were abstracted from the 2020 5-year American Community Survey. Cancer incidence and mortality data were obtained from the Centers for Disease Control and Prevention. US 2013 Rural-Urban Continuum …

Lyrical Stillness, Madhav Patel

HCA Healthcare Journal of Medicine

“Lyrical Stillness” is a poem I wrote during my radiation oncology rotation, during which I was provided the opportunity to learn more about multidisciplinary cancer care while delving deeper into radiotherapy. Cancer can be an overwhelming disease process physically, psychologically, and emotionally. Patients undergoing treatment often experience stress and anxiety with the uncertainty of their prognoses. In this poem, I describe a patient receiving radiation therapy whom I enjoyed speaking to about his favorite hobby: bird watching. During his subsequent radiation treatment sessions, I decided to play a CD of mockingbirds singing in a tropical forest, in the hopes it …

Apocrine Breast Cancer With Psammoma Bodies In A Male Patient, Alena Bashinskaya, Eric W. Baum, Michael B. Morgan

HCA Healthcare Journal of Medicine

Introduction

While male breast carcinoma is a relatively uncommon occurrence, its incidence is on the rise, potentially attributed to sporadic pathophysiological mechanisms, primarily involving hormonal imbalances. Invasive apocrine carcinoma represents a small fraction of global breast malignancies, with limited instances reported among male patients in the literature. The clinical presentation of an apocrine breast carcinoma closely resembles that of other breast cancer subtypes, as it is most often described as a solitary ulcerative nodular lesion occupying a retro-areolar region of the breast. Herein, we describe a novel case of an apocrine male breast carcinoma metastasizing to the skin, given that …

Hemophagocytic Lymphohistiocytosis In A Critically Ill Patient: A Case Report Of A Potentially Fatal Entity, Ali Khreisat, Inna Mikaella Sta Maria, Giovi Grasso-Knight, Meghan Mansour

HCA Healthcare Journal of Medicine

Background

Hemophagocytic lymphohistiocytosis (HLH) is a non-neoplastic proliferation and macrophage activation that induces cytokine-mediated bone marrow suppression and features of intense phagocytosis in the bone marrow and liver, leading to multi-organ dysfunction and ultimate failure. The diagnosis of HLH in an intensive care setting is challenging, and it is associated with high morbidity and mortality. HLH-94 is the standard protocol for treatment, consisting of dexamethasone and chemotherapy like etoposide.

Case Presentation

We present the case of a 73-year-old woman who had a prolonged hospitalization for vomiting, diarrhea, and dehydration. Her conditions were complicated by acute refractory pancytopenia on the 12th …

Successful Treatment Of An Atypical Presentation Of Disseminated Retroperitoneal Seminoma: A Case Report, Mahmoud Abd-El-Hafez, Kylie Johnson, Joe Cates, Alosh Madala

HCA Healthcare Journal of Medicine

Background

Testicular seminoma is the most common malignant tumor of the testis. It occurs at a rate of 5 per 100 000 men, primarily between the ages of 15 to 34. While seminomas typically occur in the testis, other primary sites include the mediastinum, the retroperitoneum, or other extra-gonadal sites. Due to the curable nature of the malignancy (5-year survival rate > 95%), detection at early stages of the disease is key. This case presentation explores the delayed diagnosis and treatments of an atypical presentation of disseminated seminoma.

Case Presentation

We present the unusual case of a 56-year-old male who had …

Hemophagocytic Lymphohistiocytosis Due To Ehrlichiosis: A Case Series, Ajay Iyer, Mattias D'Anna, Shruti Verma, Thomas Pritchard, Vladimir Begilman, Himal Bajracharya, Kaveh Naemi

HCA Healthcare Journal of Medicine

Background

Hemophagocytic lymphohistiocytosis (HLH) is an immunologic syndrome characterized by excessive inflammation and tissue injury due to uncontrolled activation of the phagocytic system. The underlying mechanism is a lack of downregulation of activated macrophages and lymphocytes by natural killer and T cells. Unfortunately, the diagnosis is often delayed or missed due to the rarity of the disease, decreased awareness, and clinical picture variability. Ehrlichiosis is becoming a more prevalent tick-borne illness in endemic regions and a relatively uncommon but increasingly considered cause of HLH.

Case Presentation

We describe the cases of 2 patients diagnosed with secondary HLH as per the …

Investigating The Effects Of Nosocomial Clostridioides Difficile Infection Among Acute Leukemia Patients: Insights From The 2020 National Inpatient Sample, Zubair Hassan Bodla, Mariam Hashmi, Fatima Niaz, Umer Farooq, Muhammad Jahanzeb Khalil, Farhan Khalid, Kipson Charles, Christopher L. Bray

HCA Healthcare Journal of Medicine

Background

Rising nosocomial Clostridioides difficile infections pose high risks, especially for immunocompromised leukemia patients, necessitating targeted research to enhance patient care and outcomes.

The objective of this study was to investigate the impact of nosocomial Clostridioides difficile infections (CDI) on patients hospitalized with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Methods

Our study was a retrospective analysis of adult patients hospitalized with a primary diagnosis of ALL or AML, using the Nationwide Inpatient Sample (NIS) database for 2020. Primary outcomes included the incidence of nosocomial CDI and all-cause inpatient mortality. Secondary outcomes included hospital length of stay, resource …

Disruption Of Distal Appendage Protein Cep164 Causes Skeletal Malformation In Mice, Hiroyuki Yamaguchi, Megumi Kitami, Margaret Li, Sowmya Swaminathan, Radbod Darabi, Ken-Ichi Takemaru, Yoshihiro Komatsu

Faculty, Staff and Student Publications

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 …

A Bayesian Pharmacokinetics Integrated Phase I-Ii Design To Optimize Dose-Schedule Regimes, Mengyi Lu, Ying Yuan, Suyu Liu

Faculty, Staff and Student Publications

The schedule of administering a drug has profound impact on the toxicity and efficacy profiles of the drug through changing its pharmacokinetics (PK). PK is an innate and indispensable component of the dose-schedule optimization. Motivated by this, we propose a Bayesian PK integrated dose-schedule finding (PKIDS) design to identify the optimal dose-schedule regime by integrating PK, toxicity, and efficacy data. Based on the causal pathway that dose and schedule affect PK, which in turn affects efficacy and toxicity, we jointly model the three endpoints by first specifying a Bayesian hierarchical model for the marginal distribution of the longitudinal dose-concentration process. …

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

Faculty, Staff and Student Publications

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

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

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

Predicting Kidney Graft Function And Failure Among Kidney Transplant Recipients, Yi Yao, Brad C Astor, Wei Yang, Tom Greene, Liang Li

Faculty, Staff and Student Publications

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of …

Approved Car-T Therapies Have Reproducible Efficacy And Safety In Clinical Practice, Daniel Goyco Vera, Hiral Waghela, Mohamed Nuh, Jonathan Pan, Premal Lulla

Faculty, Staff and Students Publications

CAR-T cell therapy has established itself as a highly effective treatment for hematological malignancies. There are currently six commercial CAR-T products that have been FDA approved for diseases such as B-ALL, LBCL, MCL, FL, MM, and CLL/SLL. "Real-world" studies allow us to evaluate outcomes from the general population to determine their efficacy and safety compared to those who were included in the original trials. Based on several well conducted "Real-world" studies that represent diverse populations, we report that outcomes from the original trials that led to the approval of these therapies are comparable to those in practice.

The Significance Of Aldehyde Dehydrogenase 1 In Cancers, Anh L. Nguyen, Caroline O. B. Facey, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The goal of this paper is to discuss the role of ALDH isozymes in different cancers, review advances in ALDH1-targeting cancer therapies, and explore a mechanism that explains how ALDH expression becomes elevated during cancer development. ALDH is often overexpressed in cancer, and each isoform has a unique expression pattern and a distinct role in different cancers. The abnormal expression of ALDHs in different cancer types (breast, colorectal, lung, gastric, cervical, melanoma, prostate, and renal) is presented and correlated with patient prognosis. ALDH plays a significant role in various cellular functions, such as metabolism, oxidative stress response, detoxification, and cellular …

Global Standards And Protocols For Oral Care In Pediatric Cancer Patients: Systematic Review Protocol, Meghna Pandit, Baby S. Nayak, Vasudeva K. Bhat, Suneel C. Mundkur, Judith A. Noronha, Sridhar N

Manipal Journal of Nursing and Health Sciences

Introduction Childhood cancer is a global health challenge, with over 275,000 cases annually among individuals under 19 years. Cancer treatments such as chemotherapy and radiation therapy lead to significant oral complications, including mucositis, xerostomia, and infections, adversely affecting treatment adherence and quality of life. Effective oral care is essential for mitigating these complications, particularly in resource-limited settings like India.

Objectives This systematic review aims to identify, assess, and summarize global guidelines and protocols for oral care in pediatric cancer patients, focusing on the prevention and management of oral complications during treatment.

Methods The protocol adheres to PRISMA-P guidelines and is …

A Review Of Managing Catastrophes In Robotic-Assisted Thoracic Surgery, Shamele Battan-Wraith, Kevin Wang, Ahmed Elkamel, Kameron Durante, Hope Conrad, Kayla Iannarelli, Olugbenga Okusanya, Praveen Sridhar, Stephanie G. Worrell

Department of Surgery Faculty Papers

Lung cancer is the most commonly diagnosed cancer worldwide in 2022, with over 2.5 million new cases, or 1 in 8 of all cancers diagnosed worldwide. Lung cancer is the leading cause of cancer related mortality in the United States, with non-small cell lung cancer (NSCLC) being the most prevalent type. For early-stage NSCLC, lung resection with anatomic lobectomy remains the standard of care. Robot-assisted lobectomy is gaining popularity over video-assisted thoracoscopic surgery (VATS) and open thoracotomy due to improved visualization, ergonomics, and instrumentation. Despite these advancements, intraoperative complications and a steep learning curve present significant barriers to the widespread …

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH

Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao

Faculty, Staff and Student Publications

One goal of precision medicine is to develop effective treatments for patients by tailoring to their individual demographic, clinical, and/or genetic characteristics. To achieve this goal, statistical models must be developed that can identify and evaluate potentially heterogeneous treatment effects in a robust manner. The oft-cited existing methods for assessing treatment effect heterogeneity are based upon parametric models with interactions or conditioning on covariate values, the performance of which is sensitive to the omission of important covariates and/or the choice of their values. We propose a new Bayesian nonparametric (BNP) method for estimating heterogeneous causal effects in studies with zero-inflated …

Role Of Nf2 Mutation In The Development Of Eleven Different Cancers, Shervin Hosseingholi Nouri, Vijay Nitturi, Elizabeth Ledbetter, Collin W English, Sean Lau, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Students Publications

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological …

Real-World Safety Profile Of Therapy With Ibrutinib Or Acalabrutinib In Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Ramsay Hafer, Francesco Iadevaia, Thomas Z. Rohan, Teresa Duong, Maria Poluch, Gina Keiffer, Michael Li, Andres Ferber, Luca Laurenti, Alan Khoo, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

No abstract provided.

Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons …