Loryn L. Holokai

• PhD Student at University of Cincinnati

Purpose: Pancreatic ductal adenocarcinoma (PDAC) has the lowest five-year survival rate of all cancers in the United States. Programmed death 1 receptor (PD-1)-programmed death ligand 1 (PD-L1) immune checkpoint inhibition has been unsuccessful in clinical trials. Myeloid-derived suppressor cells (MDSCs) are known to block anti-tumor CD8+ T cell im...

One of the major discoveries in stem cell research in the past decade embraces the development of "organs in a dish," also known as "organoids." Organoids are three-dimensional cellular structures derived from primary stem cells of different organ-specific cell types which are capable of self-renewal and maintenance of the parental lineages. Resear...

Background Helicobacter pylori (H. pylori) is the major risk factor for the development of gastric cancer. The progression of H. pylori induced chronic inflammation to gastric cancer may result from the aberrant expression of the cancer stem cell marker, CD44 variant isoform 9 (CD44v9). H. pylori induces reactive oxygen species (ROS) that subsequen...

Helicobacter pylori (H. pylori) is the major risk factor for the development of gastric cancer. Our laboratory has reported that the Sonic Hedgehog (Shh) signaling pathway is an early response to infection that is fundamental to the initiation of H. pylori-induced gastritis. H. pylori also induces programmed death ligand 1 (PD-L1) expression on gas...

Tumor cells expressing programmed cell death ligand 1 (PD-L1) interact with PD-1 on CD8+ cytotoxic T lymphocytes (CTLs) to inhibit CTL effector function. In gastric cancer, the mechanism regulating PD-L1 is unclear. The Hedgehog (Hh) signaling pathway is reactivated in various cancers including gastric. Here we tested the hypothesis that Hh-induced...

Tumor cells expressing programmed cell death ligand 1 (PD-L1) interact with PD-1 on CD8+ cytotoxic T lymphocytes (CTLs) to inhibit CTL effector function. In gastric cancer, the mechanism regulating PD-L1 is unclear. The Hedgehog (Hh) signaling pathway is reactivated in various cancers including gastric. Here we tested the hypothesis that Hh-induced...

Background & Aims Our goal was to develop an initial study for the proof of concept whereby gastric cancer organoids are used as an approach to predict the tumor response in individual patients. Methods Organoids were derived from resected gastric cancer tumors (huTGOs) or normal stomach tissue collected from sleeve gastrectomies (huFGOs). Organoi...

Organoid cultures generated from gastrointestinal tissues have been an invaluable advancement for in vitro studies of physiological function and disease. Here we present a comprehensive protocol for the establishment and culture of human- and mouse-derived 3-dimensional gastric organoids transferred to 2-dimensional gastric epithelial cell monolaye...

The interaction between the receptor, programmed cell death protein 1 (PD-1) and ligand, programmed cell death 1 (PD-L1) is known to inhibit CD8+ cytotoxic T lymphocyte proliferation, survival, and effector function. The result of this interaction leads to evasion of immune surveillance by tumors and subsequently cancer cell proliferation. Immunoth...

The interaction between the receptor, programmed cell death protein 1 (PD-1) and ligand, programmed cell death 1 (PD-L1) is known to inhibit CD8+ cytotoxic T lymphocyte proliferation, survival, and effector function. The result of this interaction leads to evasion of immune surveillance by tumors and subsequently cancer cell proliferation. Immunoth...

In vitro studies of gastric wound repair typically involves the use of gastric cancer cell lines in a scratch-wound assay of cellular proliferation and migration. One critical limitation of such assays, however, is their homogenous assortment of cellular types. Repair is a complex process which demands the interaction of several cell types. Therefo...

Background Helicobacter pylori (H. pylori) is the number one risk factor for gastric cancer. Currently the 5‐year‐survival rate for gastric cancer is only 29%. Our laboratory has reported that H. pylori infection results in the up‐regulation of the Sonic Hedgehog (SHH) signaling pathway mediated by an increase in the transcriptional activity of NF‐...

Background Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer‐related death in the United States. It has been shown that KRAS mutations, often found in PDAC, can lead to the up‐regulation of the expression of the cysteine/glutamate transporter xCT. Transporter xCT has been shown to allow cancer cells to evade ROS mediated...

Background Hedgehog (Hh) signaling plays a crucial role in tumor growth and chemoresistance in a variety of tumors including gastric cancer. Tumor cells often express elevated programmed cell death 1 (PD‐L1) that interacts with PD‐1 on CD8+ cytotoxic T lymphocytes (CTLs). This interaction inhibits CTL effector function, leading to immune evasion an...

Background Pancreatic Ductal Adenocarcinoma (PDAC) has a 5‐year survival rate of only 8%. This is due to the lack of targeted therapies and a poor response to chemotherapeutics. PDAC cells evade the immune response by expressing programmed death ligand 1 (PD‐L1), which is able to inhibit cytotoxic T lymphocyte (CTL) proliferation and effector funct...

Background: The Hedgehog (Hh) signaling pathway is often reactivated in various types of cancers including gastric, and hence raises the interest of targeting the Hh pathway as a potential therapeutic target for the treatment of gastric cancer. Tumor cells expressing programmed cell death 1 (PDL-1) interact with PD-1 on CD8+ cytotoxic T lymphocytes...