Life Sciences Commons^™

Expression Patterns Of M6a Rna Methylation Regulators Under Apoptotic Conditions In Various Human Cancer Cell Lines, Azime Akçaöz Alasar, Buket Sağlam, İpek Erdoğan Vatansever, Bünyamin Akgül

Turkish Journal of Biology

Background/aim: Cancer is a complex disease that involves both genetic and epigenetic factors. While emerging evidence clearly suggests that changes in epitranscriptomics play a crucial role in cancer pathogenesis, a comprehensive understanding of the writers, erasers, and readers of epitranscriptomic processes, particularly under apoptotic conditions remains lacking. The aim of this study was to uncover the changes in the expression of m6A RNA modifiers under apoptotic conditions across various cancer cell lines. Materials and methods: Initially, we quantified the abundance of m6A RNA modifiers in cervix (HeLa and ME180), breast (MCF7 and MDA-MB-231), lung (A549 and H1299), and colon (CaCo2 …

The Transmission Of Oropharyngeal Squamous Cell Carcinoma, Kunjal Patel, Aleesha Thomas

Mako: NSU Undergraduate Student Journal

The existence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has recently been found to have correlations with the Human Papillomavirus. HPV-associated OPSCC exhibits a unique method of infection and transmission and has made this branch an emerging disease in the recent decade. This systematic review of the literature was conducted to further explore research into Oropharyngeal Squamous Cell Cancer (OPSCC). Commonly referred to as “throat cancer”, this growth originates in the oropharynx. Symptoms of this condition include sore throat, lumps in the neck, and difficulty with swallowing. OPSCC has many variants but has shown a strong association with Human Papillomavirus (HPV), …

Transcription Factor Bach1 In Cancer: Roles, Mechanisms, And Prospects For Targeted Therapy, Dian Hu, Zerui Zhang, Xiangyuan Luo, Siwen Li, Junqing Jiang, Jiaqian Zhang, Zhangfan Wu, Yijun Wang, Mengyu Sun, Xiaoping Chen, Bixiang Zhang, Xiao Xu, Shuai Wang, Shengjun Xu, Yufei Wang, Wenjie Huang, Limin Xia

Faculty, Staff and Student Publications

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status …

Association Between Circulating Inflammatory Markers And Adult Cancer Risk: A Mendelian Randomization Analysis, James Yarmolinsky, Jamie W Robinson, Daniela Mariosa, Ville Karhunen, Jian Huang, Niki Dimou, Neil Murphy, Kimberley Burrows, Emmanouil Bouras, Karl Smith-Byrne, Sarah J Lewis, Tessel E Galesloot, Lambertus A Kiemeney, Sita Vermeulen, Paul Martin, Demetrius Albanes, Lifang Hou, Polly A Newcomb, Emily White, Alicja Wolk, Anna H Wu, Loïc Le Marchand, Amanda I Phipps, Daniel D Buchanan, International Lung Cancer Consortium, Practical Consortium, Sizheng Steven Zhao, Dipender Gill, Stephen J Chanock, Mark P Purdue, George Davey Smith, Paul Brennan, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Chris I Amos, Rayjean J Hung, Abbas Dehghan, Mattias Johansson, Marc J Gunter, Kostas K Tsilidis, Richard M Martin

Faculty, Staff and Student Publications

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were …

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis

Theses and Dissertations

The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …

Exploring Novel Frontiers: Leveraging Stat3 Signaling For Advanced Cancer Therapeutics, Taiwo Adesoye, Debasish Tripathy, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Signal Transducer and Activator of Transcription 3 (STAT3) plays a significant role in diverse physiologic processes, including cell proliferation, differentiation, angiogenesis, and survival. STAT3 activation via phosphorylation of tyrosine and serine residues is a complex and tightly regulated process initiated by upstream signaling pathways with ligand binding to receptor and non-receptor-linked kinases. Through downstream deregulation of target genes, aberrations in STAT3 activation are implicated in tumorigenesis, metastasis, and recurrence in multiple cancers. While there have been extensive efforts to develop direct and indirect STAT3 inhibitors using novel drugs as a therapeutic strategy, direct clinical application remains in evolution. In this …

Epstein-Barr Virus-Based Prognostic Model In Nodular Sclerosis Classic Hodgkin Lymphoma, Chen Jiang, Li-Yun Huang, Ji-Hao Zhou, Zhi-Ming Li, Yu Wang, Shuo Li, Jian-Chang Fu, Qi-Tao Huang, Qin Yan, Yu-Yuan Huang, Min Zuo, Shimin Hu, Robert Peter Gale, Yang Liang, Jing-Ping Yun, Yu-Hua Huang

Faculty, Staff and Student Publications

The role of Epstein-Barr virus (EBV) in lymphoma cells of nodular sclerosis classic Hodgkin lymphoma (NScHL) is controversial. Our aim was to explore this and establish a clinically feasible model for risk stratification. We interrogated data from 542 consecutive subjects with NScHL receiving ABVD therapy and demonstrated EBV-infection in their lymphoma cells with EBV-encoded small RNAs (EBERs) in situ hybridization. Subjects were divided into training and validation datasets. As data from the training dataset suggested EBERs-positivity was the only independent prognostic factor for both progression-free survival (PFS) and overall survival (OS), we developed corresponding prognostic models based on it. Our …

Class Ii Hla-Drb4 Is A Predictive Biomarker For Survival Following Immunotherapy In Metastatic Non-Small Cell Lung Cancer, Cindy Y Jiang, Lili Zhao, Michael D Green, Shashidhar Ravishankar, Andrea M H Towlerton, Anthony J Scott, Malini Raghavan, Matthew F Cusick, Edus H Warren, Nithya Ramnath

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated …

Deciphering The Double-Edged Action Of Sting Pathway In Cancer, Neelabh Datta

Inquiry: The University of Arkansas Undergraduate Research Journal

Cancer cells have unstable chromosomes and damaged DNA, which can activate the cellular alarm system cGAS-STING. This mechanism detects DNA in the incorrect location (the cytosol) and produces type I interferons, which can recruit immune cells to combat cancer. However, certain tumours can bypass or use this mechanism for their own benefit. This short article examines how cGAS-STING influences the different cells of the tumour microenvironment (TME), and how it can have both anti-tumour and pro-tumour effects. It also demonstrates how additional STING signals can cause inflammation and contribute to cancer growth. To employ cGAS-STING against cancer, it is critical …

Locus-Specific Differential Expression Of Human Satellite Sequences In The Nuclei Of Cancer Cells And Heat-Shocked Cells, Christina Rabeler, N. Paterna, Rajiv Potluri , '20, Lia R. D’Alessandro , '21, Anusha Bhatia , '24, Shu Yi Chen , '24, Johanna Lee , '23, Bereketab Abeje , '23, Benjamin Lipchin , '25, B. R. Carone, Dawn M. Carone

Biology Faculty Works

Human satellites (HSats) are pericentric, tandemly repeating satellite DNA sequences in the human genome. While silent in normal cells, a subset of HSat2 noncoding RNA is expressed and accumulates in the nucleus of cancer cells. We developed a FISH-based approach for identification of the distribution of three subfamilies of HSat2 (A1, A2, B) sequences on individual human chromosomes. Further, using the HSat subfamily annotations in the T2T completed centromere satellite (CenSat) sequence, we isolated, defined and mapped differentially expressed sequence variants of nuclear-restricted HSat2 and HSat3 RNA from cancer cell lines and heat-shocked cells. We identified chromosome-specific and subfamily-specific expression …

Proteomic Analysis Of Wnt Signaling And Metabolism Of Fibrolamellar Hepatocellular Carcinoma, James Knox

Student Theses and Dissertations

Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer that primarily affects young adults and adolescents.Although characterized as a subvariant of hepatocellular carcinoma (HCC), we have shown it is distinct based on its pathogenesis, patient population and drug response. Our lab has identified a fusion gene DNAJB1::PRKACA that is found in almost all FLC tumor samples sequenced to date. The fusion gene when expressed in mouse liver is sufficient to generate FLC, and elimination of the fusion transcript kills human tumors. The fusion results from a ~400kb deletion on chromosome 19, beginning after the first exon ofDNAJB1, which …

Characterizing Sex Differences In Hpv Negative Head And Neck Squamous Cell Carcinoma, Sarah Barclay

Dissertations and Theses

It is now widely accepted that peripheral solid tumors are infiltrated by nerves. This infiltration of malignancies by nerves is referred to as tumor innervation. The Vermeer laboratory studies tumor innervation primarily in head and neck squamous cell carcinoma using a syngeneic cell line representing a mutationally-induced form of the disease; these cells are called MOC2-7 cells. In addition to defining the molecular consequences of tumor-infiltrating nerves on disease, the lab also focuses on their influence on behavior. This is important as cancer patients have a significantly higher incidence of depression and anxiety as compared to the population at large. …

Investigating The Mechanisms For Priming And Maintaining Tumor Ag Specific Cd8+ T Cell Responses In The Context Of Cd4-Depletion, Delaney E. Ramirez

Dartmouth College Ph.D Dissertations

Achieving durable, systemic CD8+ T cell responses against tumors is an imperative goal in treating cancer. However, suppressive cells, including Foxp3+CD4+ regulatory T cells (Tregs) are widely recognized to inhibit CD8+ T cell activity. For nearly two decades, anti-CD4 treatment has been used to eliminate Tregs and induces durable tumor antigen (Ag) specific CD8+ T cells, despite also depleting Foxp3-negative conventional CD4+ T (Tconv) cells. However, the underlying mechanism of anti-CD4 efficacy is not understood. In Chapter Three, we look beyond Treg depletion and investigate the potential contributions of other factors including homeostatic space, depletion of CD4+ APCs, and presence …

Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly

Theses and Dissertations--Toxicology and Cancer Biology

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms which can be classified as intrinsic or extrinsic resistance. The intrinsic resistance is usually present prior to any treatment whereas the extrinsic resistance develops as a result of exposure to some kind of therapy. In order to target these “therapy resistant” tumor cells an unbiased screen of an FDA-approved drug library against cancer cells was performed. This was followed by synthesis of chemical analogs of the most effective drug.

The studies led to the identification of a derivative of the antihistamine drug ebastine, designated Super-ebastine …

"Hunter-Killer" Peptoid-Peptide Conjugate To Target And Eliminate Cancer Stem Cells, Breanne F. Mcelderry

Chemistry Theses

In the contemporary paradigm concerning the emergence of therapy-resistant recurrent cancer, recent studies posit the existence of a limited population of self-renewing malignant progenitors known as cancer stem cells (CSCs). The presence of CSCs explains why tumors often relapse despite clinical remission with initial therapeutic interventions. Consequently, the development of innovative therapeutic modalities specifically tailored to target and eliminate CSCs represents a highly promising strategy for eradicating cancer without the risk of recurrence. In previous research, we successfully developed a synthetic peptoid-based ligand CL-1-19-1 that selectively binds to CSC over non-CSC. However, CL-1-19-1 did not exhibit any significant inhibitory effect …

Machine Learning As A Tool For Early Detection: A Focus On Late-Stage Colorectal Cancer Across Socioeconomic Spectrums, Hadiza Galadima, Rexford Anson-Dwamena, Ashley Johnson, Ghalib Bello, Georges Adunlin, James Blando

Community & Environmental Health Faculty Publications

Purpose: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. Methods: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. Results: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, …

Mechanistic Insights Into Direct Interactions That Mediate The Activity Of Dot1l Complex In Mll-Rearranged Leukemia, Ali Cihan

Student Theses and Dissertations

Acute leukemia can arise from the translocation-mediated fusion of the N terminus of the Mixed Lineage Leukemia (MLL) protein to various partner proteins. Although more than 60 different translocation-based fusion proteins have been identified, fusion partners such as AF9, AF10, and ENL constitute the majority of the MLL-rearranged leukemia cases; additionally, these fusion partners are also a part of the DOT1L (disruptor of telomeric silencing 1-like) complex. Aberrant histone H3 Lysine 79 (H3K79) methylation catalyzed by DOT1L was shown to be crucial for the maintenance of MLL-rearranged leukemia. DOT1L is the only known H3K79 methyltransferase, and further, a DOT1L inhibitor …

Rna Therapeutics For Fibrolamellar Hepatocellular Carcinoma, Christoph Neumayer

Student Theses and Dissertations

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer characterized by a recurrent fusion of the heat shock protein DNAJB1 and the catalytic subunit of protein kinase A (PRKACA). Due to limited efficacy of conventional treatments such as chemotherapy and radiation my work explored new therapeutic options. As DNAJB1::PRKACA is known to initiate tumorigenesis, I reasoned that it would be an ideal target for a therapeutic. However, it was not known if FLC tumors are still dependent on DNAJB1::PRKACA or if cells achieved independence of the initial oncogene. To test if FLC is dependent on the oncokinase I screened short …

Near-Infrared Paired-Agent Imaging For In Vivo Quantification Of Receptor Occupancy In Tumor, Yichen Feng

Dartmouth College Ph.D Dissertations

Accurate assessment of drug receptor occupancy (RO) holds significant importance in both drug development and personalized medicine, as it facilitates quantitative characterization of dose-response relationship for a given drug. This information not only aids appropriate dose selection for clinical trials but also guides personalized dose optimization in precision medicine.

Molecular imaging, utilizing receptor-specific imaging agents for tissue visualization, has emerged as the major option for in vivo measurement of tissue RO. Nonetheless, the abnormal yet complex structure and hemodynamics of tumors often lead to substantial non-specific uptake and retention of imaging agents, thus introducing significant bias to RO measurements. To …

Synthetic Strategies Toward The Development Of Stable Gold-Based Anticancer Agents And Their Mechanistic Insight, Adedamola Arojojoye

Theses and Dissertations--Chemistry

Despite notable advancements in the design and synthesis of novel chemotherapeutic drugs, cancer continues to be a leading cause of death in the United States. Metallodrugs, especially Au complexes, have played a prominent role in the search for the next generation of chemotherapeutic agents. Herein, I report on the synthetic strategies towards the rational design of stable Au (Au)-based agents, study their reactivity in biological environment, and offer insights into the cytotoxic mechanism of action in cancer. Chemotherapeutic Au compounds exist mainly in +I or +III oxidation states. Repurposing of the Au(I) FDA approved auranofin for the treatment of diseases …

A Prospective Multi-Centered Registry-Based Observational Study For Patients With Cancer: Design And Rationale For Korean Medicine Cancer Registry (Kmcare), Jee Young Lee, Hayun Jin, Su Bin Park, Eun Hye Kim, Jee-Hyun Yoon, Seong Woo Yoon

Faculty, Staff and Student Publications

Background: Cancer is one of the leading causes of death in most countries with an expected increased burden on healthcare systems. Since integrative medical treatments are not collected within the scope of existing cancer registries, the establishment of the Korean Medicine Cancer Registry (KMCARE), gathering integrative therapies, including conservative care and Korean medicine, is warranted.

Methods: A prospective observational study based on the registry will be conducted in 5 Korean medical hospitals. A total of 650 eligible participants undergoing Korean medicine treatments within 1 month of a diagnosis of lung, colorectal, stomach, or breast cancer are anticipated to be enrolled …

Harnessing Microrna-Enriched Extracellular Vesicles For Liquid Biopsy, Song Yi Ko, Wonjae Lee, Honami Naora

Faculty, Staff and Student Publications

Extracellular microRNAs (miRNAs) can be detected in body fluids and hold great potential as cancer biomarkers. Extracellular miRNAs are protected from degradation by binding various proteins and through their packaging into extracellular vesicles (EVs). There is evidence that the diagnostic performance of cancer-associated extracellular miRNAs can be improved by assaying EV-miRNA instead of total cell-free miRNA, but several challenges have hampered the advancement of EV-miRNA in liquid biopsy. Because almost all types of cells release EVs, cancer cell-derived EVs might constitute only a minor fraction of EVs in body fluids of cancer patients with low volume disease. Furthermore, a given …

Immune-Related Adverse Event In The Emergency Department: Methodology Of The Immune-Related Emergency Disposition Index (Iredi), Cielito C Reyes-Gibby, Jeffrey M Caterino, Christopher J Coyne, Demetrios N Kyriacou, Aiham Qdaisat, Jennifer Mcquade, Dwight H Owen, Jason J Bischof, Sanjay Shete, Sai-Ching Jim Yeung

Faculty, Staff and Student Publications

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the …

A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer

Faculty, Staff and Student Publications

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing …

Expert-Centered Evaluation Of Deep Learning Algorithms For Brain Tumor Segmentation, Katharina V Hoebel, Christopher P Bridge, Sara Ahmed, Oluwatosin Akintola, Caroline Chung, Raymond Y Huang, Jason M Johnson, Albert Kim, K Ina Ly, Ken Chang, Jay Patel, Marco Pinho, Tracy T Batchelor, Bruce R Rosen, Elizabeth R Gerstner, Jayashree Kalpathy-Cramer

Faculty, Staff and Student Publications

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D'Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). …

Immune Checkpoint Inhibitor Therapy For Advanced Cutaneous Squamous Cell Carcinoma In Australia: A Retrospective Real World Cohort Study, Luke S. Mclean, Annette M. Lim, Mathias Bressel, Jenny Lee, Rahul Ladwa, Alexander D. Guminski, Brett Hughes, Samantha Bowyer, Karen Briscoe, Samuel Harris, Craig Kukard, Rob Zielinski, Muhammad Alamgeer, Matteo Carlino, Jeremy Mo, John J. Park, Muhammad A. Khattak, Fiona Day, Danny Rischin

Research outputs 2022 to 2026

Objectives: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. Study design: Retrospective observational study; review of patient records in fifteen Australian institutions. Setting, participants: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 – 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. Main outcome measures: Best overall response rate (ORR) according to …

Exploratory Pilot Study To Characterize The Immune Landscapes Of Malignant Pleural Effusions And Their Corresponding Primary Tumors From Patients With Breast Carcinoma And Lung Adenocarcinoma, Caddie Laberiano-Fernandez, Qiong Gan, Sophia Mei Wang, Auriole Tamegnon, Ignacio Wistuba, Esther Yoon, Sinchita Roy-Chowdhuri, Edwin Roger Parra

Faculty, Staff and Student Publications

Introduction: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples.

Materials and methods: We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion-free survival.

Results: No MPE samples had positive programmed death-ligand 1 expression in malignant cells, although 3 of …