Rejection resistant CD30.CAR-modified Epstein-Barr virus-specific T cells as an off-the-shelf platform for CD30 lymphoma.

Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.

A Costimulatory CAR Improves TCR-based Cancer Immunotherapy.

T-cell receptors (TCR) recognize intracellular and extracellular cancer antigens, allowing T cells to target many tumor antigens. To sustain proliferation and persistence, T cells require not only signaling through the TCR (signal 1), but also costimulatory (signal 2) and cytokine (signal 3) signaling. Because most cancer cells lack costimulatory molecules, TCR engagement at the tumor site results in incomplete T-cell activation and transient antitumor effects.

Single-cell transcriptomics identifies multiple pathways underlying antitumor function of TCR- and CD8αβ-engineered human CD4 T cells.

Transgenic coexpression of a class I-restricted tumor antigen-specific T cell receptor (TCR) and CD8αβ (TCR8) redirects antigen specificity of CD4 T cells. Reinforcement of biophysical properties and early TCR signaling explain how redirected CD4 T cells recognize target cells, but the transcriptional basis for their acquired antitumor function remains elusive. We, therefore, interrogated redirected human CD4 and CD8 T cells by single-cell RNA sequencing and characterized them experimentally in bulk and single-cell assays and a mouse xenograft model.

MiR-21 Expression in Wilms' Tumor.

Background And Objective: Wilms' tumor (WT) is the most common genitourinary tract tumor in children. MicroRNAs (miRNAs) are small non-coding RNAs; their role in the pathogenesis of many types of human cancers has been identified. We aimed to evaluate the expression of miR-21, a well-known oncomir, in WT tissue samples which is a very common urinary tract malignancy in children.

OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers.

The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies.

Separation of microRNA 21 as a cancer marker from glioblastoma cell line using molecularly imprinted polymer coated on silica nanoparticles.

In this study for the first time, microRNA was separated on the basis of affinity for a phase made using molecular imprinting technology. We describe the synthesis and preliminary testing of molecularly imprinted polymers for separation of the microRNA 21 from the lysate obtained from brain cancer cell line. A new molecularly imprinted polymer was synthesized using microRNA 21 and dopamine as the template and functional monomer, respectively.

MicroRNAs contribution in tumor microenvironment of esophageal cancer.

Background: miRNAs have recently been implicated in tumor's microenvironment remodeling and tumor-stromal cells interactions. We have previously reported a signaling role for miR-21, as a secretory molecule released by cancer associated fibroblasts (CAF) adjacent to esophagus tumor cells.

Objective: To discover other potential signaling miRNAs, we employed a co-culture system of esophageal cancer cell line and normal fibroblasts to mimic the tumor microenvironment.

Simultaneous Underexpression of let-7a-5p and let-7f-5p microRNAs in Plasma and Stool Samples from Early Stage Colorectal Carcinoma.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer death worldwide. Early detection of CRC can improve patient survival rates; thus, the identification of noninvasive diagnostic markers is urgently needed. MicroRNAs (miRNAs) have extensive potential to diagnose several diseases, including cancer.

Downregulation of Plasma MiR-142-3p and MiR-26a-5p in Patients With Colorectal Carcinoma.

Background: Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer.

Epstein-Barr Virus MicroRNAs are Expressed in Patients with Chronic Lymphocytic Leukemia and Correlate with Overall Survival.

Although numerous studies highlighted the role of Epstein-Barr Virus (EBV) in B-cell transformation, the involvement of EBV proteins or genome in the development of the most frequent adult leukemia, chronic lymphocytic leukemia (CLL), has not yet been defined. We hypothesized that EBV microRNAs contribute to progression of CLL and demonstrated the presence of EBV miRNAs in B-cells, in paraffin-embedded bone marrow biopsies and in the plasma of patients with CLL by using three different methods (small RNA-sequencing, quantitative reverse transcription PCR [q-RT-PCR] and miRNAs in situ hybridization [miRNA-ISH]). We found that EBV miRNA BHRF1-1 expression levels were significantly higher in the plasma of patients with CLL compared with healthy individuals (p < 0 · 0001).

miRNA therapeutics in cardiovascular diseases: promises and problems.

microRNAs (miRNAs) are a novel class of non-coding RNAs which found their way into the clinic due to their fundamental roles in cellular processes such as differentiation, proliferation, and apoptosis. Recently, miRNAs have been known as micromodulators in cellular communications being involved in cell signaling and microenvironment remodeling. In this review, we will focus on the role of miRNAs in cardiovascular diseases (CVDs) and their reliability as diagnostic and therapeutic biomarkers in these conditions.

Tracking miRNAs' footprints in tumor-microenvironment interactions: Insights and implications for targeted cancer therapy.

In the past decades, cancer medicine studies have mainly focused on tumor cell biology as the main promoter of solid tumor progression. However, tumor biology does not explain the intertwinement and ambiguity of the tumors' territory. Recently, the approach of understanding cancer has shifted from investigating the biology of tumor cells to studying the microenvironment surrounding them.

Decreased expression of fecal miR-4478 and miR-1295b-3p in early-stage colorectal cancer.

Background: Colorectal cancer (CRC) is a major cause of cancer-related deaths world-wide. Detection of molecular markers in stool samples is a promising strategy for CRC screening. MicroRNAs (miRNAs) are short, non-coding RNA molecules that are commonly dysregulated in neoplasia.

Cell-free microRNAs as cancer biomarkers: the odyssey of miRNAs through body fluids.

Cell-free microRNAs (cfmiRNAs), also known as extracellular or secretory microRNAs, are an emerging class of miRNAs that are released or secreted by cells. These miRNAs are transferred through various body fluids. A growing body of research has recently revealed that cancer cells also secrete their distinctive cfmiRNAs to the extracellular environment highlighting the contribution of cfmiRNAs to cancer progression.

Expression, tissue distribution and function of miR-21 in esophageal squamous cell carcinoma.

Objective: MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.

Design: MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR.

Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia.

Noncoding RNAs play a pivotal role in the pathogenesis of chronic lymphocytic leukemia (CLL). We hypothesized that microRNAs (miRs) are involved in the transition from monoclonal B-cell lymphocytosis (MBL) to CLL and tested miR-15a/16-1 cluster, miR-21, and miR-155 expression in purified B cells of normal individuals, individuals with MBL, and patients with CLL. When we analyzed 224 samples from 2 independent training and validation cohorts, we found that miR-155 was overexpressed in B cells from individuals with MBL, and even more so in B cells from patients with CLL, when compared with B cells from normal individuals.

Evaluating the expression of oct4 as a prognostic tumor marker in bladder cancer.

Objectives: The key transcriptional regulator Oct4 is one of the self-renewal and differentiation-related factors in cancer stem cells, where it maintains "stemness" state. Cancer stem cells have been identified in a variety of solid malignancies. They are a small population of tumor cells with stem cell characteristics, which are a likely cause of relapse in cancer patients.

MicroRNAs as cancer biomarkers.

MicroRNAs (miRNAs) are attractive, short, non-coding RNAs widely studied for their fundamental roles in tissue homeostasis, cell proliferation, and dysregulation in cancer. A vast majority of investigations and technical improvements have focused on miRNAs' tumor-specific expression patterns, which provide novel molecular biomarkers for cancer detection and targeted therapies. In this review, we focus on recent achievements in biomarker validation and potential for cancer treatment, with special trend in non-invasive strategies to evaluate miRNAs, especially for diagnostic and prognostic applications.

Expression of survivin and its spliced variants in bladder tumors as a potential prognostic marker.

Introduction: Survivin, a novel inhibitor of apoptosis, is re-expressed in a vast majority of human cancers and is widely considered as a diagnostic marker of cancers. Survivin protein regulates both cell division and apoptosis. There are at least 5 spliced variants of the gene with different subcellular localization and anti-apoptotic property.