Dll3

A new molecular subtype classification method has been proposed for small cell lung carcinoma (SCLC). However, little is known about the differences between the pure (P-SCLC) and combined subtypes (C-SCLC). We aimed to compare the molecular subtype expression and genomic profiling in terms of clinical relevance between the two groups. 154 surgically resected SCLCs were analyzed for protein expression of four subtypes (ASCL1, NEUROD1, POU2F3, and YAP1) and two predictive markers (DLL3 and MYC) by immunohistochemistry (IHC)...

INTRODUCTION: Notch signaling is crucial during pregnancy with ability to regulate angiogenesis and inflammatory response. Considering the enigmatic importance of Notch signaling in pregnancy including placenta development, gestational disorders and adverse pregnancy; we performed experimental analysis to identify the Notch receptor-ligands association with Preterm delivery (PTD) and linked complication. METHOD: A total of 245 cases [Term n = 135 and Preterm n = 110] were enrolled for the study from Northeast Indian Population...

AIMS: To characterise the clinicopathological and genetic characteristics of gastric neuroendocrine tumour G3 (gNET G3) and to compare them with those of gastric neuroendocrine carcinoma (gNEC) and gNET G2. METHODS AND RESULTS: A total of 115 gastric neuroendocrine neoplasms (NENs) were included, of which gNET G3 was different from gNET G1/G2 in terms of tumour location (P = 0.029), number (P = 0.003), size (P = 0.010), the Ki67 index (P < 0...

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells...

Chemotherapy is the standard therapy for small cell lung cancer (SCLC), but relapse is common and the 2-year survival rate remains low. Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single-cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in five chemotherapy-naive patients identified upregulation of Notch-inhibiting genes, such as DLL3 and HES6...

INTRODUCTION: Spondylocostal dysostosis (SCD) is characterized by multiple vertebral abnormalities associated with abnormalities of the ribs. Five genes causative for the disease have been identified. These include DLL3 (OMIM *602768), MESP2 (OMIM #608681), LFNG (OMIM #609813), TBX6 (OMIM *602427), and HES7 (OMIM *608059). METHODS: In the current study, we investigated a Pakistani consanguineous family segregating spondylocostal dysotosis. Whole-exome sequencing (WES) followed by Sanger sequencing was performed using DNA of affected and unaffected individuals to identify pathogenic variant(s)...

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Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA...

OBJECTIVE: To evaluate the biological and immunological significance of DLL3 expression in different tumor tissues and provide insight into the role of DLL3 in tumor immunotherapy. MATERIAL AND METHODS: RNA expression and clinical data of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were acquired, and we employed couple of bioinformatics methods to investigate the potential biological and immunological role DLL3, including pan-cancer expression, survival analysis, GSVA and it's correlation with immune infiltration scores, tumor mutation burden, tumor microsatellite instability...

ALK-negative anaplastic large cell lymphoma (ALCL) cases with 6p25.3 rearrangement are characterized by peculiar morphological and immunohistochemical features compare to 6p25.3-negative ALK-negative ALCL cases. A subgroup of 6p25.3-positive ALK-negative ALCL cases show the t(6,7)(p25.3;q32.3) rearrangement. Aims: To analyse the differences between 6p25.3-rearranged cases with and without t(6,7)(p25.3;q32.3). Using RNA-sequencing we studied a series of 17 samples showing 6p25.3-rearrangement, identified by FISH, consisting of seven systemic and eight primary cutaneous cases including two examples of secondary skin involvement by systemic ALCL...

Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c...

Alveolar echinococcosis (AE) is a lethal helminthic liver disease caused by persistent infection with Echinococcus multilocularis (E. multilocularis). Although more and more attention has been paid to the macrophages in E. multilocularis infection, the mechanism of macrophage polarization, a critical player in liver immunity, is seldom studied. NOTCH signaling is involved in cell survival and macrophage-mediated inflammation, but the role of NOTCH signaling in AE has been equally elusive. In this study, liver tissue samples from AE patients were collected and an E...

Patients with small cell lung cancer (SCLC) generally have a poor prognosis and a median overall survival of only about 13 months, indicating the urgent need for novel therapies. Delta-like protein 3 (DLL3) has been identified as a tumor-specific cell surface marker on neuroendocrine cancers, including SCLC. In this study, we developed a chimeric antigen receptor (CAR) against DLL3 that displays antitumor efficacy in xenograft and murine SCLC models. CAR T cell expression of the proinflammatory cytokine IL-18 greatly enhanced the potency of DLL3-targeting CAR T cell therapy...

INTRODUCTION: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab...

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES)...

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Uveitis is an immune eye disease that can seriously impair vision. Glucocorticoids (GCS ) have been extensively used to treat uveitis, though the mechanisms have not been fully elucidated. In this study, we investigated the regulatory effects of prednisone acetate (PA) on the Th1/Th2 and Th17/Treg balance in experimental autoimmune uveitis (EAU) through modulating the Notch signaling pathway. Briefly, Lewis rats were randomly divided into the normal control (NC), EAU, and EAU + PA groups. Rats in EAU and EAU + PA groups were induced EAU, while those in the EAU + PA group were treated with PA...

INTRODUCTION: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer frequently seen after prolonged treatment of castration resistant prostate cancer (CRPC). NEPC has become increasingly prevalent over the last 20 years, with a poor prognosis caused by a late diagnosis and limited treatment options. Recent advances in PET/CT imaging and targeted radioimmunotherapy are promising, but more research into additional treatment options is needed. AREAS COVERED: The aim of this review is to analyze the current imaging and treatment options for NEPC, and to highlight future potential treatment strategies...

PURPOSE: Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Delta-like ligand 3 (DLL3) is highly expressed on SCLC and several other types of neuroendocrine cancers, with limited normal tissue RNA expression in brain, pituitary, and testis, making it a promising CAR T-cell target for SCLC and other solid tumor indications. EXPERIMENTAL DESIGN: A large panel of anti-DLL3 scFv-based CARs were characterized for both in vitro and in vivo activity...

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC. PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety...