Dr. Azhar Saeed

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Academic Career Length

8Years (2019-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

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28 August 2023 in Cancers

Journal Article

Anti-Inflammatory and Immune Properties of Polyunsaturated Fatty Acids (PUFAs) and Their Impact on Colorectal Cancer (CRC) Prevention and Treatment

Colorectal cancer (CRC) remains a leading cause of death from cancer worldwide, with increasing incidence in the Western world. Diet has become the focus of research as a significant risk factor for CRC occurrence, and the role of dietary polyunsaturated fatty acids (PUFAs) has become an area of interest given their potential role in modulating inflammation, particularly in the pro-carcinogenic inflammatory environment of the colon. This work reviews the main types of PUFAs, their characteristics, structure, and physiologic role. We then highlight their potential role in preventing CRC, their signaling function vis-à-vis tumorigenic signaling, and their subsequent potential role in modulating response to different treatment modalities. We review pre-clinical and clinical data and discuss their potential use as adjunct therapies to currently existing treatment modalities. Given our understanding of PUFAs’ immune and inflammation modulatory effects, we explore the possible combination of PUFAs with immune checkpoint inhibitors and other targeted therapies.

19 November 2023 in International Journal of Molecular Sciences

Journal Article

Cancer-Associated Fibroblasts in Gastrointestinal Cancers: Unveiling Their Dynamic Roles in the Tumor Microenvironment

Gastrointestinal cancers are highly aggressive malignancies with significant mortality rates. Recent research emphasizes the critical role of the tumor microenvironment (TME) in these cancers, which includes cancer-associated fibroblasts (CAFs), a key component of the TME that have diverse origins, including fibroblasts, mesenchymal stem cells, and endothelial cells. Several markers, such as α-SMA and FAP, have been identified to label CAFs, and some specific markers may serve as potential therapeutic targets. In this review article, we summarize the literature on the multifaceted role of CAFs in tumor progression, including their effects on angiogenesis, immune suppression, invasion, and metastasis. In addition, we highlight the use of single-cell transcriptomics to understand CAF heterogeneity and their interactions within the TME. Moreover, we discuss the dynamic interplay between CAFs and the immune system, which contributes to immunosuppression in the TME, and the potential for CAF-targeted therapies and combination approaches with immunotherapy to improve cancer treatment outcomes.

19 October 2023 in Cancers

Journal Article

Characterization of Age-Associated, Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Survival

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Background: Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help with patient selection. Methods: We built a multicenter, international retrospective study of 885 patients (<80 years: n = 417, 47.12%; ≥80 years: n = 468, 52.88%) with different tumor types treated with ICIs between 2011 and 2021 from 11 academic centers in the U.S. and Europe. The main outcome measures were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) stratified by age and circulating inflammatory levels (neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII)). Results: Patients ≥80 years with low NLR (NLR-L) and SII (SII-L) had significantly higher ORR (vs. high NLR [NLR-H], p < 0.01 and SII-H, p < 0.05, respectively). At median follow-ups (13.03 months), and compared to SII-H, patients with SII-L had significantly longer median PFS and OS in patients <80 (p < 0.001), and ≥80 years (p < 0.001). SII-L was independently associated with longer PFS and OS (HR: 0.61 and 0.62, respectively, p < 0.01). Conclusion: Lower inflammation pre-ICI initiation may predict an improved response and survival in geriatric patients with cancer.

1 July 2019 in Molecular Immunology

Journal Article

The mouse intron-nested gene, Israa, is expressed in the lymphoid organs and involved in T-cell activation and signaling

Noureddine Ben Khalaf

Wedad Al-Mashoor

Azhar Saeed

Dalal Al-Mehatab

Safa Taha

M.Dahmani Fathallah

We have previously reported Israa, immune-system-released activating agent, as a novel gene nested in intron 8 of the mouse Zmiz1 gene. We have also shown that Israa encodes for a novel FYN-binding protein and might be involved in the regulation of T-cell activation. In this report, we demonstrate that Israa gene product regulates the expression of a pool of genes involved in T-cell activation and signaling. Real time PCR and GFP knock-in expression analysis showed that Israa is transcribed and expressed in the spleen mainly by CD3(+)CD8(+) cells as well as in the thymus by CD3(+) (DP and DN), CD4(+)SP and CD8(+)SP cells at different developmental stages. We also showed that Israa is downregulated in T-cells following activation of T-cell receptor. Using yeast two-hybrid analysis, we identified ELF1, a transcription factor involved in T-cell regulation, as an ISRAA-binding partner. Transcriptomic analysis of an EL4 cell line overexpressing ISRAA revealed differential expression of several genes involved in T-cell signaling, activation and development. Among these genes, Prkcb, Mib2, Fos, Ndfip2, Cxxc5, B2m, Gata3 and Cd247 were upregulated whereas Itk, Socs3, Tigit Ifng, Il2ra and FoxJ1 were downregulated. Our findings support the existence in mouse of a novel FYN-related T-cell regulation pathway involving the product of an intron-nested gene.

22 April 2022 in American Journal of Medical Genetics Part A

Journal Article

Third reported patient with RAP1B‐related syndromic thrombocytopenia and novel clinical findings

RAP1B is a RAS-superfamily small GTP-binding protein involved in numerous cell processes. Pathogenic gain-of-function variants in this gene have been associated with RAP1B-related syndromic thrombocytopenia, an ultrarare disorder characterized by hematologic abnormalities, neurodevelopmental delays, growth delay, and congenital birth defects including cardiovascular, genitourinary, neurologic, and skeletal systems. We report a 23-year-old male with a novel, de novo RAP1B gain-of-function variant identified on genome sequencing. This is the third reported case which expands the molecular and phenotypic spectrum of RAP1B-related syndromic thrombocytopenia.

12 March 2019 in Current Colorectal Cancer Reports

Journal Article

The Duplex Interaction of Microbiome with Chemoradiation and Immunotherapy: Potential Implications for Colorectal Cancer

Azhar Saeed

Fariha Eshrat

Shahid Umar

Anwaar Saeed

About Me

Dr. Azhar Saeed is a Gastrointestinal and Molecular Pathologist and an Assistant Professor of Pathology and Laboratory Medicine at the Robert Larner, M.D. College of Medicine at The University of Vermont. She obtained her Bachelor of Basic Medical Sciences (BSc) and Doctor of Medicine (MD) degrees from Arabian Gulf University, followed by a Master of Science (MSc) in Cancer Chemical Biology from the University of Michigan, Ann Arbor. Dr. Saeed completed her residency in Anatomic and Clinical Pathology at the University of Kansas Medical Center, then pursued fellowships in Molecular Genetic Pathology at the University of Minnesota and Gastrointestinal, Hepatic, and Pancreaticobiliary Pathology at the University of Utah. She is board-certified in Anatomic Pathology, Clinical Pathology, and Molecular Genetic Pathology, and she is a Fellow of the College of American Pathologists (FCAP). Her research focuses on understanding the genomic characteristics that shape tumor microenvironment phenotypes in gastrointestinal (GI) and hepatobiliary cancers. Specifically, she investigates the molecular predictors of response and resistance to targeted immunotherapy combination regimens in hepatobiliary and microsatellite-stable GI malignancies. Dr. Saeed leads translational research initiatives aimed at identifying novel molecular and prognostic predictors of treatment response and actively publishes in this field.

Dr. Azhar Saeed

Dr. Azhar Saeed

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About Me