Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation.

Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples.

Genomic studies of cancer cell alterations, such as mutations, copy number variations (CNVs), and translocations, greatly promote our understanding of the genesis and development of cancers. However, the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties. To explore the 3D genome structure in clinical lung cancer, we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer, combining with RNA sequenceing analysis.

The abnormal function of CD39 regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells.

The pretreatment platelet count is an independent predictor of tumor progression in patients undergoing transcatheter arterial chemoembolization with hepatitis B virus-related hepatocellular carcinoma.

Aim: To explore the prognostic value of the pretreatment platelet (PLT) count in patients undergoing transcatheter arterial chemoembolization (TACE) with hepatocellular carcinoma (HCC).

Materials & Methods: We prospectively analyzed 317 hepatitis B virus-related HCC patients undergoing TACE. Time to progression (TTP) was selected to evaluate the clinical significance of PLT level in HCC patients.

Serological cytokine profiles of cardiac rejection and lung infection after heart transplantation in rats.

Background: Allograft rejection and infection are the major sources of morbidity and mortality after heart transplant. Early differential diagnosis is clinically crucial but difficult. The aim of the study was to examine serum cytokine profiles associated with each entity and whether such profiles could help to differentiate between them.

Regulatory Roles of Osteopontin in Production of Monocyte-Origin MCP-1.

Osteopontin (OPN), expressed by various immune cells, plays a critical role in leukocyte migration. Although OPN was found to selectively induce the expression of proinflammatory chemokines, the molecular mechanisms that control OPN gene expression and its underlying mechanism for migration and recruitment of inflammatory cells remain largely unknown. In this study, real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine OPN and monocyte chemoattractant protein 1 (MCP-1) expression.

Aberrant phosphorylation of signal transducer and activator of transcription 3 protein of the CD4+ T cells in patients with primary immune thrombocytopenia.

: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count of which dysfunctional cellular immunity in its pathogenesis. Signal transducer and activator of transcription 3 (STAT3) is critical for the differentiation of T cells. The present study was aimed to investigate the STAT3 protein phosphorylation of CD4 T cells in ITP patients.

Outcomes of adjuvant treatments for resectable intrahepatic cholangiocarcinoma: Chemotherapy alone, sequential chemoradiotherapy, or concurrent chemoradiotherapy.

Background: Prospective randomized trials have not been used to evaluate the efficacy of adjuvant therapies after intrahepatic cholangiocarcinoma (ICC) resection.

Methods: We analyzed data from the Taiwan Cancer Registry database of ICC patients receiving resection. To compare outcomes, patients with ICC were enrolled and categorized into the following adjuvant treatment modality groups: group 1, concurrent chemoradiotherapy (CCRT); group 2, sequential chemotherapy (CT) and radiotherapy (RT); and group 3, CT alone.

Distinct alterations of CD68CD163 M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment.

Background: Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP.

Methods: Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs.

Lung Cancer Heterogeneity and New Strategies for Drug Therapy.

Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system.

Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

Background: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients.

Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma.

Background & Aims: Identifying target genetic mutations in hepatocellular carcinoma (HCC) for therapy is made challenging by intratumoral heterogeneity. Circulating cell-free DNAs (cfDNA) may contain a more complete mutational spectrum compared to a single tumor sample. This study aimed to identify the most efficient strategy to identify all the mutations within heterogeneous HCCs.

Regulatory roles of epigenetic modulators, modifiers and mediators in lung cancer.

Lung cancer as the leading cause of cancer-related deaths can be initiated and progressed by the interaction between dynamically genetic and epigenetic elements, although mechanisms mediating lung cancer development and progression remain unclear. Tumor progenitor genes may contribute to lung carcinogenesis and cancer progression, are epigenetically disrupted at the early stages of malignancies even before mutations, and alter cell differentiation throughout tumor evolution. The present review explores potential roles and mechanisms of epigenetic modulators, modifiers and mediators in the development of lung cancer.

Roles of Telocytes in the Development of Angiogenesis.

Telocytes are cells with telopodes, which distinguish them from other interstitial cells. According to the study of lung, it was confirmed that telocytes were mainly distributed in the alveolar interstitial tissues connected tightly with alveolar epithelia cells and participated in the structure of air-blood barrier, in the small vein and bronchioles and in the interstitial space of smooth muscle participated in the frame structure of the blood and bronchioles. Telocytes are positive to CD34 and C-kit which expressed on the surface of hemopoietic stem cells, and are proposed to participate in the angiogenesis.

The History of Telocyte Discovery and Understanding.

Telocytes (TCs) are identified as a peculiar cell type of interstitial cells in various organs. The typical features of TCs from the other cells are the extending cellular process as telopodes with alternation of podomeres and podoms. Before the year of 2010, TCs were considered as interstitial Cajal-like cells because of the similar morphology and immunohistochemical features with interstitial cells of Cajal which were found more than 100 years ago and considered to be pacemakers for gut motility.

Regulatory mechanisms of TGF-β1-induced fibrogenesis of human alveolar epithelial cells.

Pulmonary fibrosis is characterized by an extensive activation of fibrogenic cells and deposition of extracellular matrix (ECM). Transforming growth factor (TGF)-β1 plays a pivotal role in the pathogenesis of pulmonary fibrosis, probably through the epithelial- to-mesenchymal transition (EMT) and ECM production. The present study investigates potential mechanism by which TGF-β1 induces EMT and ECM production in the fibrogenesis of human lung epithelial cells during pulmonary fibrosis.

Role of osteopontin in lung cancer evolution and heterogeneity.

Patients with lung cancer still have high mortality, recurrence rate after adjuvant treatment, and poor five-year survival rates, despite of advances in multidisciplinary anti-cancer therapies, e.g. chemotherapy, radiotherapy and targeted therapies, It depends upon the presence of intratumoral heterogeneity and complexity of lung cancer.

Role of epigenetics in lung cancer heterogeneity and clinical implication.

Lung cancer, as a highly heterogeneous disease, can be initiated and progressed through the interaction between permanent genetic mutations and dynamic epigenetic alterations. However, the mediating mechanisms of epigenetics in cancer heterogeneity remain unclear. The evolution of cancer, the existence of cancer stem cells (CSCs) and the phenomenon of epithelial-mesenchymal transition (EMT) have been reported to be involved in lung cancer heterogeneity.

Telocytes and lung disease.

Telocytes (TCs) represent a new distinct type of interstitial cells found in many organs, including lungs. TCs are mainly defined by a small cellular body from which arise very long (hundreds of micrometers) extensions named telopodes. During the last years, TCs were characterized in respect with their microRNA profiles, gene features and proteome signatures.

Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics.

Gene mutation-based and specific therapies in precision medicine.

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application.

Production of CCL20 from lung cancer cells induces the cell migration and proliferation through PI3K pathway.

Tumour inflammatory microenvironment is considered to play a role in the sensitivity of tumour cells to therapies and prognosis of patients with lung cancer. The expression of CCL20, one of the critical chemoattractants responsible for inflammation cells recruitment, has been shown overexpressed in variety of tumours. This study aimed at investigating potential mechanisms of CCL20 function and production in human non-small cell lung cancer (NSCLC).