RESUMO
BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoproliferative disorder (LPD) involving the gastrointestinal tract is rarely observed in individuals with normal immunity. The atypical clinical, colonoscopic manifestations often confuse clinicians, leading to misdiagnosis and delays in the treatment. CASE PRESENTATION: Herein, we reported on a single case of a patient with gastrointestinal symptoms. Several colonoscopies showed multiple irregular ulcerations, while biopsies showed colitis with infiltration of neutrophils or lymphocytes. After 2 months follow-up, the patient was diagnosed with the extranodal NK/T-cell lymphoma, nasal type, and was treated with thalidomide. Later on, a second check was performed on his first pathological sample. Immunohistochemistry revealed EBV associated NK/T-cell LPD. CONCLUSIONS: Multiple, multiform, and segmental gastrointestinal ulcers should be an indication for EBV infection, regardless of the presence of fever, lymphadenopathy, and hepatosplenomegaly. If EBV-associated NK/T-cell LPD is considered, serum EBV-DNA should be measured, and the tissue obtained by biopsy should be carefully analyzed for a positive expression of the EBER marker.
Assuntos
Infecções por Vírus Epstein-Barr , Gastroenteropatias , Transtornos Linfoproliferativos , Células T Matadoras Naturais , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Humanos , Transtornos Linfoproliferativos/diagnósticoRESUMO
Liquid-liquid phase separation (LLPS) is a physiological phenomenon that parallels the mixing of oil and water, giving rise to compartments with diverse physical properties. Biomolecular condensates, arising from LLPS, serve as critical regulators of gene expression and control, with a particular significance in the context of malignant tumors. Recent investigations have unveiled the intimate connection between LLPS and cancer, a nexus that profoundly impacts various facets of cancer progression, including DNA repair, transcriptional regulation, oncogene expression, and the formation of critical membraneless organelles within the cancer microenvironment. This review provides a comprehensive account of the evolution of LLPS from the molecular to the pathological level. We explore the mechanisms by through which biomolecular condensates govern diverse cellular physiological processes, encompassing gene expression, transcriptional control, signal transduction, and responses to environmental stressors. Furthermore, we concentrate on potential therapeutic targets and the development of small-molecule inhibitors associated with LLPS in prevalent clinical malignancies. Understanding the role of LLPS and its interplay within the tumor milieu holds promise for enhancing cancer treatment strategies, particularly in overcoming drug resistance challenges. These insights offer innovative perspectives and support for advancing cancer therapy.
Assuntos
Neoplasias , Separação de Fases , Humanos , Neoplasias/genética , Neoplasias/terapia , Reparo do DNA , Junções Comunicantes , Oncogenes , Microambiente Tumoral/genéticaRESUMO
Large gastric folds (LGF) can be caused by benign conditions as well as malignancies. Unfortunately, endoscopic features and biopsy results are often equivocal, making the diagnosis and management of large gastric folds difficult. Polyposis syndromes encompass a group of conditions in which multiple gastrointestinal polyps occur in the lumen of the gut. Large gastric folds are extremely rare in these syndromes. We present the case of a patient with polyposis who was found to have large gastric folds in the entire gastric fundus and body, mimicking malignancy. The patient's medical history and endoscopic ultrasonography (EUS) with mucosal resection confirmed the diagnosis of a pre-malignant disease. The lesion was monitored by serial endoscopic ultrasonography and biopsy, abdominal computed tomography (CT), and positron emission and computed tomography (PET-CT) for 6 years. The lesion remained stable, with the exception of abnormal fluorodeoxyglucose uptake on PET-CT in the gastric folds, which was determined to be a false-positive sign. To date, the patient remains healthy. We further discuss the mechanisms underlying the formation of large gastric folds caused by polyposis syndromes. Helicobacter pylori (H. pylori) or cytomegalovirus (CMV) is unnecessary for this progression. Immunohistochemistry (IHC) staining suggested that overexpression of transforming growth factor alpha (TGF-alpha) and down-regulation of myocyte enhancer-binding factor 2 (MEF2) may be involved in this case.
Assuntos
Mucosa Gástrica/patologia , Pólipos/patologia , Gastropatias/patologia , Adulto , Biópsia , Endossonografia , Mucosa Gástrica/diagnóstico por imagem , Humanos , Masculino , Gastropatias/diagnóstico por imagem , SíndromeRESUMO
Transcriptional deregulation, a cancer cell hallmark, is driven by epigenetic abnormalities in the majority of brain tumors, including adult glioblastoma and pediatric brain tumors. Epigenetic abnormalities can activate epigenetic regulatory elements to regulate the expression of oncogenes. Superenhancers (SEs), identified as novel epigenetic regulatory elements, are clusters of enhancers with cell-type specificity that can drive the aberrant transcription of oncogenes and promote tumor initiation and progression. As gene regulators, SEs are involved in tumorigenesis in a variety of tumors, including brain tumors. SEs are susceptible to inhibition by their key components, such as bromodomain protein 4 and cyclin-dependent kinase 7, providing new opportunities for antitumor therapy. In this review, we summarized the characteristics and identification, unique organizational structures, and activation mechanisms of SEs in tumors, as well as the clinical applications related to SEs in tumor therapy and prognostication. Based on a review of the literature, we discussed the relationship between SEs and different brain tumors and potential therapeutic targets, focusing on glioblastoma.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Criança , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Oncogenes , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Regulação Neoplásica da Expressão GênicaRESUMO
Digestive system tumors include malignancies of the stomach, pancreas, colon, rectum, and the esophagus, and are associated with high morbidity and mortality. Aberrant epigenetic modifications play a vital role in the progression of digestive system tumors. The aberrant transcription of key oncogenes is driven by super-enhancers (SEs), which are characterized by large clusters of enhancers with significantly high density of transcription factors, cofactors, and epigenetic modulatory proteins. The SEs consist of critical epigenetic regulatory elements, which modulate the biological characteristics of digestive system tumors including tumor cell identity and differentiation, tumorigenesis, environmental response, immune response, and chemotherapeutic resistance. The core transcription regulatory loop of the digestive system tumors is complex and a high density of transcription regulatory complexes in the SEs and the crosstalk between SEs and the noncoding RNAs. In this review, we summarized the known characteristics and functions of the SEs in the digestive system tumors. Furthermore, we discuss the oncogenic roles and regulatory mechanisms of SEs in the digestive system tumors. We highlight the role of SE-driven genes, enhancer RNAs (eRNAs), lncRNAs, and miRNAs in the digestive system tumor growth and progression. Finally, we discuss clinical significance of the CRISPR-Cas9 gene editing system and inhibitors of SE-related proteins such as BET and CDK7 as potential cancer therapeutics.
Assuntos
Neoplasias do Sistema Digestório , Elementos Facilitadores Genéticos , Humanos , Fatores de Transcrição , Regulação da Expressão Gênica , Oncogenes , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/genéticaRESUMO
BACKGROUND: Invasion and metastasis are the hallmarks of advanced gastric cancer progression. Therefore, it is urgent to overcome metastasis in order to improve the survival of gastric cancer patients. AIMS: This study aimed to examine the expression of ZEB2 in gastric cancer samples and analyze its correlation with clinicopathologic features. In addition, the molecular mechanism by which ZEB2 contributes to gastric cancer metastasis will be explored. METHODS: ZEB2 expression in clinical gastric cancer samples was evaluated by immunohistochemical analysis. ZEB2 was knocked-down in HGC27 gastric cancer cells by shRNA and the effects on cell invasion and migration were examined by in vitro cell invasion and migration assays. The expression of epithelial marker E-cadherin, mesenchymal markers fibronecin and vimentin, and MMPs was detected by western blot analysis. RESULTS: The expression of ZEB2 was positively correlated with the depth of invasion, lymph node metastasis and TNM stage. In addition, patients with positive ZEB2 expression showed a significantly shorter overall survival time than did patients with negative ZEB2. shRNA mediated knockdown of ZEB2 resulted in reduced invasion and migration of HGC27 cells, along with the upregulation of E-cadherin and downregulation of fibronecin, vimentin, MMP2, and MMP9. CONCLUSIONS: ZEB2 expression is closely associated with the clinicopathological parameters of gastric cancer. ZEB2 promotes gastric cancer cell migration and invasion at least partly via the regulation of epithelial-mesenchymal transition. ZEB2 is a potential target for gene therapy of aggressive gastric cancer.
Assuntos
Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio , Proteínas Repressoras , Neoplasias Gástricas , Estômago/patologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Metástase Linfática , Masculino , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Prognóstico , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Análise Serial de Tecidos , Vimentina/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
Circular RNAs (circRNAs) play an important role in cancer development and progression by regulating gene expression. The present study aimed to investigate the function of circRNA_100859 in colon cancer. circRNA expression profiles from a human circRNAs chip were analyzed. The effects of circRNA_100859 on cell proliferation and apoptosis were assessed in vitro and interactions between circRNA_100859 and its micro (mi)RNA and target genes were analyzed. The diagnostic and prognostic significance of circRNA_100859 was also investigated. It was identified that circRNA_100859 was overexpressed in colon cancer tissues and promoted cell proliferation and inhibited cell apoptosis. Additionally, bioinformatics and a dual-luciferase reporter assay confirmed that circRNA_100859 acted as a miR-217 sponge, and miR-217 directly targeted hypoxia-inducible factor (HIF)-1α. Rescue assays demonstrated that HIF-1α protein and mRNA expression levels and cell proliferation were regulated by the circRNA_100859/miR-217 axis (P<0.05). Furthermore, statistical analysis showed that the circRNA_100859-miR-217-HIF-1α axis was associated with Tumor-Node-Metastasis (TNM) stage, histological grade, and KRAS mutations, and also showed high diagnostic and prognostic value for patients with colon cancer (P<0.05). Therefore, it was concluded that circRNA_100859 functions as an oncogene in colon cancer by sponging the miR-217-HIF-1α pathway. In addition, the circRNA_100859-miR-217-HIF-1α axis may serve as a novel diagnostic and prognostic biomarker for patients with colon cancer.