Medicine and Health Sciences Commons^™

Uncloaking Cell-Impermeant Gold Nanorods Via Tumor Microenvironmental Cathepsin B Facilitates Cancer Cell Penetration And Potent Radiosensitization, Subhiksha Raghuram, Yuri Mackeyev, Jessica Symons, Yasmin Zahra, Valeria Gonzalez, Krishnan K Mahadevan, Katherinne I Requejo, Anton Liopo, Paul Derry, Eugene Zubarev, Onur Sahin, Joseph Byung-Kyu Kim, Pankaj K Singh, Sang Hyun Cho, Sunil Krishnan

Student and Faculty Publications

Major impediments to conveyance of intravenously administered drugs to tumors are biofouling, opsonization, and rapid clearance from the circulation by macrophages and reticuloendothelial phagocytes. Cloaking nanoparticles with stealth epilayers partly overcomes these hurdles but it also foils interactions with tumor cells. Here, we describe the synthesis, characterization, and validation of smart gold nanorods (GNRs) that spontaneously transform from inert passengers in the blood stream to active cell-penetrating nanoparticles within tumors to potently sensitize tumors to radiation therapy. Intrinsically cationic and cell-penetrating GNRs were shielded from phagocytosis with a cloaking polyethylene glycol epilayer containing an intervening cleavable peptide. In the absence …

Autologous Humanized Mouse Models To Study Combination And Single-Agent Immunotherapy For Colorectal Cancer Patient-Derived Xenografts, Preeti Kanikarla Marie, Alexey V Sorokin, Lea A Bitner, Rebecca Aden, Michael Lam, Ganiraju Manyam, Melanie N Woods, Amanda Anderson, Anna Capasso, Natalie Fowlkes, Michael J Overman, David G Menter, Scott Kopetz

Student and Faculty Publications

Designing studies of immunotherapy is limited due to a lack of pre-clinical models that reliably predict effective immunotherapy responses. To address this gap, we developed humanized mouse models of colorectal cancer (CRC) incorporating patient-derived xenografts (PDX) with human peripheral blood mononuclear cells (PBMC). Humanized mice with CRC PDXs were generated via engraftment of autologous (isolated from the same patients as the PDXs) or allogeneic (isolated from healthy donors) PBMCs. Human T cells were detected in mouse blood, tissues, and infiltrated the implanted PDXs. The inclusion of anti-PD-1 therapy revealed that tumor responses in autologous but not allogeneic models were more …

Guanylyl Cyclase C As A Diagnostic And Therapeutic Target In Colorectal Cancer, Adi Caspi, Ariana A. Entezari, Madison Crutcher, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Colorectal cancer remains a major cause of mortality in the USA, despite advances in prevention and screening. Existing therapies focus primarily on generic treatment such as surgical intervention and chemotherapy, depending on disease severity. As personalized medicine and targeted molecular oncology continue to develop as promising treatment avenues, there has emerged a need for effective targets and biomarkers of colorectal cancer. The transmembrane receptor guanylyl cyclase C (GUCY2C) regulates intestinal homeostasis and has emerged as a tumor suppressor. Further, it is universally expressed in advanced metastatic colorectal tumors, as well as other cancer types that arise through intestinal metaplasia. In …

Assessment Of A Size-Based Method For Enriching Circulating Tumour Cells In Colorectal Cancer, Sai Shyam Vasantharajan, Edward Barnett, Elin S. Gray, John L. Mccall, Euan J. Rodger, Michael R. Eccles, Fran Munro, Sharon Pattison, Aniruddha Chatterjee

Research outputs 2022 to 2026

Circulating tumour cells (CTC) from solid tumours are a prerequisite for metastasis. Isolating CTCs and understanding their biology is essential for developing new clinical tests and precision oncology. Currently, CellSearch is the only FDA (U.S. Food and Drug Administration)-approved method for CTC enrichment but possesses several drawbacks owing to a reliance on the epithelial cell adhesion molecule (EpCAM) and a resource-intensive nature. Addressing these shortcomings, we optimised an existing size-based method, MetaCell, to enrich CTCs from blood of colorectal cancer (CRC) patients. We evaluated the ability of MetaCell to enrich CTCs by spiking blood with CRC cell lines and assessing …

Increasing Colorectal Cancer Screening Adherence: A Scoping Review, Megan E. Billingsley Bsn, Rn, Tiameria T. Ford Bsn, Rn, Mikayla E. Vican Bsn, Rn, Diana Dedmon Dnp, Aprn, Fnp-Bc

Doctor of Nursing Practice Projects

Purpose/Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Rates have steadily increased in recent years due to high rates of obesity, smoking, and sedentary lifestyles. Screening for the disease can lead to early detection and reduced morbidity/mortality, yet screening rates remain low. Existing literature is extensive in discussing methods to increase CRCS adherence; therefore, a scoping review allows for increased understanding of barriers to CRCS and how to address those barriers to increase screening compliance.

Methods A literature search was completed from September 2020 to October 2021. Multiple databases were used, including …

Targeting Gastrointestinal Cancers With Chimeric Antigen Receptor (Car)-T Cell Therapy, Ross E Staudt, Robert D Carlson, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The immune system is capable of remarkably potent and specific efficacy against infectious diseases. For decades, investigators sought to leverage those characteristics to create immune-based therapies (immunotherapy) that might be far more effective and less toxic than conventional chemotherapy and radiation therapy for cancer. Those studies revealed many factors and mechanisms underlying the success or failure of cancer immunotherapy, leading to synthetic biology approaches, including CAR-T cell therapy. In this approach, patient T cells are genetically modified to express a chimeric antigen receptor (CAR) that converts T cells of any specificity into tumor-specific T cells that can be expanded to …

Endoscopic Management Of Complex Colorectal Polyps: Current Insights And Future Trends, Rupinder Mann, Mahesh Gajendran, Chandraprakash Umapathy, Abhilash Perisetti Md, Hermant Goyal, Shreyas Saligram, Juan Echavarria

PCI Publications and Projects

Most colorectal cancers arise from adenomatous polyps and sessile serrated lesions. Screening colonoscopy and therapeutic polypectomy can potentially reduce colorectal cancer burden by early detection and removal of these polyps, thus decreasing colorectal cancer incidence and mortality. Most endoscopists are skilled in detecting and removing the vast majority of polyps endoscopically during a routine colonoscopy. Polyps can be considered “complex” based on size, location, morphology, underlying scar tissue, which are not amenable to removal by conventional endoscopic polypectomy techniques. They are technically more challenging to resect and carry an increased risk of complications. Most of these polyps were used to …

Geographic Determinants Of Colorectal Cancer In Louisiana, Denise Danos, Claudia Leonardi, Xiao Cheng Wu

School of Public Health Faculty Publications

Purpose: Currently, rural residents in the United States (US) experience a greater cancer burden for tobacco-related cancers and cancers that can be prevented by screening. We aim to characterize geographic determinants of colorectal cancer (CRC) incidence in Louisiana due to rural residence and other known geographic risk factors, area socioeconomic status (SES), and cultural region (Acadian or French-speaking). Methods: Primary colorectal cancer diagnosed among adults 30 years and older in 2008–2017 were obtained from the Louisiana Tumor Registry. Population and social and economic data were obtained from US Census American Community Survey. Rural areas were defined using US Department of …

Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva

Surgery Faculty Publications

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …