The switch of tumor cells from an epithelial to a mesenchymal-like phenotype [designated as epithelial-to-mesenchymal transition (EMT)] is known induce cell motility and invasiveness, therefore promoting metastasis solid carcinomas. Although multiple studies have focused on elucidating the signaling events that initiate this phenotypic switch, there has been so far no characterization pattern soluble mediators released by undergoing EMT, potential impact could remodeling microenvironment....

Metastatic disease is responsible for the majority of human cancer deaths. Understanding molecular mechanisms metastasis a major step in designing effective therapeutics. Here we show that T-box transcription factor Brachyury induces tumor cells epithelial-mesenchymal transition (EMT), an important progression primary tumors toward metastasis. Overexpression carcinoma induced changes characteristic EMT, including upregulation mesenchymal markers, downregulation epithelial and increase cell...

The epithelial-mesenchymal transition (EMT) is emerging as a critical factor for the progression and metastasis of carcinomas, well drug resistance. T-box transcription Brachyury has been recently characterized driver EMT in human carcinoma cells. purpose this study was to characterize potential target lung cancer therapy.The expression evaluated by PCR immunohistochemistry tumors adult normal tissues. gene copy number promoter methylation status were analyzed tumor tissues with various...

Aberrant expression of the T-box transcription factor brachyury in human carcinomas drives phenomenon epithelial-mesenchymal transition (EMT), a phenotypic modulation that facilitates tumor dissemination and resistance to conventional therapies, including chemotherapy radiotherapy. By generating isogenic cancer cell lines with various levels expression, we demonstrate high also significantly reduce susceptibility cells lysis by both antigen-specific T natural killer cells. Our results...

The T-box transcription factor Brachyury, a molecule frequently detected in human cancers but seldom found normal adult tissue, has recently been characterized as driver of the epithelial-to-mesenchymal switch carcinomas. In current investigation, we present data demonstrating that two different lung carcinoma models expression Brachyury strongly correlates with increased vitro resistance to cytotoxic therapies, such chemotherapy and radiation. We also demonstrate treatment selects for tumor...

The epithelial–mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. transcription factor brachyury recently described a driver of EMT human carcinoma cells. Brachyury mRNA protein expression was analyzed breast carcinomas benign tissues. role prognosis resistance the ability brachyury-specific T cells to lyse were also evaluated. Kaplan–Meier analyses used evaluate association between survival. All statistical tests...

Despite the success of immune checkpoint blockade therapy in treatment certain cancer types, only a small percentage patients with solid malignancies achieve durable response. Consequently, there is need to develop novel approaches that could overcome mechanisms tumor resistance inhibition. Emerging evidence has implicated phenomenon plasticity or acquisition mesenchymal features by epithelial cells, as an mechanism.

Epithelial-mesenchymal transition (EMT) is a molecular and cellular program in which epithelial cells lose their well-differentiated phenotype adopt mesenchymal characteristics. This process, occurs naturally during embryogenesis, has also been shown to be associated with cancer progression tumor recurrence following conventional therapies. Brachyury transcription factor that mediates EMT development, aberrantly expressed various human cancers where it promotes cell EMT, metastatic...

Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its physiological role in normal tissues, CSF1/CSF1 receptor axis known be overexpressed many tumor types associated with poor prognosis. High levels CSF1 within microenvironment have been shown recruit reeducate macrophages produce factors that promote invasiveness accelerate metastasis....

The embryonic T-box transcription factor brachyury is aberrantly expressed in a range of human tumors. Previous studies have demonstrated that driver the epithelial-mesenchymal transition (EMT), process associated with cancer progression. Brachyury expression tumor cells enhances invasiveness vitro and metastasis vivo, induces resistance to various conventional therapeutics including chemotherapy radiation. These characteristics, selective for types vs. normal adult tissues, make an...

Purpose: The transcription factor brachyury has been shown in preclinical studies to be a driver of the epithelial-to-mesenchymal transition (EMT) and resistance therapy human tumor cells. This study describes characterization Modified Vaccinia Ankara (MVA) vector-based vaccine expressing transgenes for three costimulatory molecules (B7.1, ICAM-1, LFA-3, designated TRICOM) phase I with this vaccine.Experimental Design: Human dendritic cells (DC) were infected MVA-brachyury-TRICOM define...

Abstract The epithelial–mesenchymal transition (EMT) is a process associated with the metastasis of solid tumors as well acquisition resistance to standard anticancer modalities. A major initiator EMT in carcinoma cells TGF-β, which has been shown induce expression several transcription factors ultimately responsible for initiating and maintaining program. We have previously identified Brachyury, T-box factor, an inducer mesenchymal features human cells. In this study, potential link between...

A signaling pathway that is frequently deregulated in human carcinomas and has been explored as a therapeutic target involves the activation of epidermal growth factor receptor (EGFR). Inhibition EGFR via small molecule inhibitors erlotinib gefitinib commonly results tumor resistance, even patients with EGFR-mutant tumors initially show substantial clinical responses. This study was designed to broaden our understanding molecular mechanisms acquired resistance lung cancer cells bearing wild...

The conversion of tumor cells from an epithelial to a mesenchymal-like phenotype, via process designated as the epithelial-mesenchymal transition (EMT), is known mediate resistance variety cell death inducers, including cytotoxic effector immune cells. goal this study was identify and potentially repurpose FDA-approved compounds capable reducing mesenchymal features human lung carcinoma cells, which could be used in combination with immunotherapies or chemotherapeutic strategies improve...

A prospective population-based surveillance system was established to characterize the epidemiology of cat-scratch disease (CSD) among residents Connecticut who were reported state health department with a diagnosis suspected CSD. During 1992 and 1993, 246 persons met case definition, for an average statewide annual incidence 3.7/100,000 persons. The median age patients CSD 14 years (range, 1-64), 52% female. age-specific attack rate highest < 10 (9.3/100,000) decreased increasing age....

Immunotherapy has demonstrated clinical efficacy in subsets of patients with solid carcinomas. Multimodal therapies using agents that can affect different arms the immune system and/or tumor microenvironment (TME) might increase responses.We demonstrate entinostat, a class I histone deacetylase inhibitor, enhances antitumor IL15 superagonist N-803 plus vaccine 4T1 triple-negative breast and MC38-CEA colon murine carcinoma models. A comprehensive gene-expression analysis was performed...

Patients diagnosed with triple-negative breast cancer (TNBC) have a high rate of tumor metastasis and poor prognosis. The treatment option for these patients is currently chemotherapy, which results in very low response rates. Strategies that exploit the immune system now shown ability to improve survival several types. Identifying potential targets therapeutic interventions an important step developing novel treatments TNBC. In this study, silico analysis publicly available datasets...

SCLC is a highly aggressive tumor with 5-year survival rate of less than 6%. A heterogeneous disease, classified into four subtypes that include tumors neuroendocrine and non-neuroendocrine features. Immune checkpoint blockade has been recently added for the frontline treatment SCLC; however, this therapy only led to modest clinical improvements. The lack benefit in cancer type known have high mutational burden attributed poor T-cell infiltration low expression MHC-class I most tumors. In an...

Abstract Purpose: Endogenous retroviruses (ERVs) are remnants of retrovirus germline infections that occurred over the course evolution and constitute between 5-8% human genome. While ERVs tend to be epigenetically silenced in normal adult tissues, they often overexpressed carcinomas may represent novel immunotherapeutic targets. However, therapeutic cancer vaccines targeting have not been assessed clinically. For first time, this study characterizes ERV envelope protein ERVMER34-1 as target...

Background Endogenous retroviruses (ERVs) are remnants of retrovirus germline infections that occurred over the course evolution and constitute between 5% 8% human genome. While ERVs tend to be epigenetically silenced in normal adult tissues, they often overexpressed carcinomas may represent novel immunotherapeutic targets. This study characterizes ERV envelope protein ERVMER34-1 as a target for therapeutic cancer vaccine. Methods The expression multiple healthy tissues was assessed, its...

Abstract Endogenous retroviruses (ERV) are the genetic remnants of in which proviral sequences integrated into germline cells our ancestors. Although vast majority ERV have accumulated mutations over course human evolution, some still contain open reading frames encoding full-length retroviral proteins. These typically epigenetically silenced healthy adult tissues. However, epigenetic dysregulation cancer results aberrant expression ERVs multiple types. Therefore, represent a class...