Diethylhexyl phthalate induces immune dysregulation and is an environmental immune disruptor.

Diethylhexyl phthalate (DEHP) is the most abundant phthalate compound in the environment, and has been linked with multiple human diseases. The immune system is closely associated with the occurrence and progression of various diseases. However, minimal research has addressed the impact of DEHP on the immune system.

Antiangiogenic Treatment Facilitates the Abscopal Effect of Radiation Therapy Combined With Anti-PD-1 in Hepatocellular Carcinoma.

Purpose: Metastasis is one of the most important factors contributing to poor prognosis in hepatocellular carcinoma. Radiation therapy (RT), along with its induced abscopal effect, is a promising treatment for metastatic patients. However, the incidence of abscopal effect in clinical practice is rare, even when RT is combined with immune checkpoint inhibitors (ICIs).

Polystyrene microplastics aggravate radiation-induced intestinal injury in mice.

Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 μg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14.

Single-cell transcriptomics reveal the microenvironment landscape of perfluorooctane sulfonate-induced liver injury in female mice.

Epidemic and animal studies have reported that perfluoroalkyl and polyfluoroalkyl substances (PFASs) are strongly associated with liver injury; however, to date, the effects of PFASs on the hepatic microenvironment remain largely unknown. In this study, we established perfluorooctane sulfonic acid (PFOS)-induced liver injury models by providing male and female C57BL/6 mice with water containing PFOS at varying doses for 4 weeks. Hematoxylin and eosin staining revealed that PFOS induced liver injury in both sexes.

Single-cell Transcriptomic Analysis Reveals an Immunosuppressive Network Between POSTN CAFs and ACKR1 ECs in TKI-resistant Lung Cancer.

Background/aim: Tyrosine kinase inhibitor (TKI) therapy, a principal treatment for advanced non-small cell lung cancer (NSCLC), frequently encounters the development of drug resistance. The tumor microenvironment (TME) plays a critical role in the progression of NSCLC, yet the relationship between endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) subpopulations in TKI treatment resistance remains largely unexplored.

Materials And Methods: The BioProject database PRJNA591860 project was used to analyze scRNA-seq data including 49 advanced-stage NSCLC samples across three different time points: pre-targeted therapy (naïve), post-partial response (PR) to targeted therapy, and post-progressive disease (PD) stage.

UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism.

The oncogene protein ubiquitin-conjugating enzyme E2T (UBE2T) is reported to be upregulated in hepatocellular carcinoma (HCC) and correlated with poor clinical outcomes of HCC patients. However, the underlying mechanism by which UBE2T exerts its oncogenic function in HCC remains largely unexplored. In this study, in vitro and in vivo experiments suggested that UBE2T promoted HCC development including proliferation and metastasis.

Wnt/β-catenin inhibitor ICG-001 enhances the antitumor efficacy of radiotherapy by increasing radiation-induced DNA damage and improving tumor immune microenvironment in hepatocellular carcinoma.

Background And Purpose: Radiotherapy (RT) has a promising anti-tumor effect depending on its effects on both cancer cells and tumor immune microenvironment (TIME). As one of the most common alterations in hepatocellular carcinoma (HCC), wnt/β-catenin pathway activation, has been reported to induce radioresistance and suppressive TIME. In this study, we aim to explore the effect of wnt/β-catenin inhibitor ICG-001 on radiosensitivity and RT-related TIME of HCC and the underlying mechanism.

UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation.

Background: Radioresistance is the major obstacle in radiation therapy (RT) for hepatocellular carcinoma (HCC). Dysregulation of DNA damage response (DDR), which includes DNA repair and cell cycle checkpoints activation, leads to radioresistance and limits radiotherapy efficacy in HCC patients. However, the underlying mechanism have not been clearly understood.

Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study.

Background: Genetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed cell death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis to develop a genomic mutation signature (GMS) and predict the response to anti-PD-(L)1 therapy.

Methods: In this multicohort analysis, 316 patients with non-squamous NSCLC treated with anti-PD-(L)1 from three independent cohorts were included in our study.

ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma.

Background: Radioimmunotherapy has a promising antitumor effect in hepatocellular carcinoma (HCC), depending on the regulatory effect of radiotherapy on tumor immune microenvironment. Ionizing radiation (IR)-induced DNA damage repair (DDR) pathway activation leads to the inhibition of immune microenvironment, thus impairing the antitumor effect of radioimmunotherapy. However, it is unclear whether inhibition of the DDR pathway can enhance the effect of radioimmunotherapy.

[Long noncoding RNA UFC1 promotes metastasis and invasion of hepatocellular carcinoma cells via GSK-3β/β-catenin axis].

Objective: To explore the role of Long noncoding RNA UFC1 (lincRNA-UFC1) in modulating the metastasis and invasion of hepatocellular carcinoma (HCC) cells and the underlying mechanism.

Methods: Human HCC cell line Huh7 was infected with the lentiviral vector carrying lincRNA-UFC1 to obtain a cell line with lincRNA-UFC1 overexpression. A short hairpin RNA (shRNA) targeting lincRNA-UFC1 was delivered in human HCC BEL-7402 cells via a lentiviral vector to obtain a cell line with lincRNA-UFC1 knockdown.

Knockdown of inhibitsproliferation and invasion and promotes senescence of hepatocellular carcinoma cells.

Uveal autoantigen with coiled-coil domains and ankyrin repeats (UACA/Nucling), has been reported to be upregulated in various cancers. However, its expression and function have not been studied in hepatocellular carcinoma (HCC). In the present study, expression of UACA was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the results revealed that UACA was upregulated in 23 cases of HCC compared with paired corresponding non-tumor liver tissues.

Identification and Functional Characterization of Long Non-coding RNA as a Tumor Suppressor for Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) have recently been identified as critical regulators in tumor initiation and development. However, the function of lncRNAs in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of lncRNA in HCC.

miR-139-5p inhibits aerobic glycolysis, cell proliferation, migration, and invasion in hepatocellular carcinoma via a reciprocal regulatory interaction with ETS1.

Cancer cells have metabolic features that allow them to preferentially metabolize glucose through aerobic glycolysis, providing them with a progression advantage. However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has not been extensively investigated. We addressed this in the present study by examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model.

Up-regulation of LncRNA SNHG20 Predicts Poor Prognosis in Hepatocellular Carcinoma.

Recent studies indicated that long noncoding RNAs (lncRNAs) played important regulatory roles in carcinogenesis and cancer progression. However, the contribution of small nucleolar RNA host gene 20 (SNHG20) to cancer development remains largely unknown. The aim of the study is to investigate the expression of SNHG20 and its clinical significance in hepatocellular carcinoma (HCC).

UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3β/β-catenin pathway.

Increasing evidence has shown that UBE2T plays an important role in genomic integrity and carcinogenesis; however, its role in nasopharyngeal carcinoma (NPC) has not been investigated. Here, we evaluated the clinicopathological significance of UBE2T in NPC and its underlying mechanisms. Using immunohistochemical analysis of UBE2T expression in NPC samples, we demonstrated that UBE2T is highly expressed in NPC tissues, which correlated with the T/M classification, skull invasion, and poor prognosis.

SNHG3 correlates with malignant status and poor prognosis in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) have been found dysregulated in human disease, especially in cancer. Small nucleolar RNA host gene 3 (SNHG3) is an lncRNA whose potential function and mechanism in hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to determine SNHG3 expression and its clinical significance in HCC.

The long intergenic noncoding RNA UFC1, a target of MicroRNA 34a, interacts with the mRNA stabilizing protein HuR to increase levels of β-catenin in HCC cells.

Background & Aims: Altered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development. We investigated the mechanisms by which the long intergenic noncoding RNA UFC1 (lincRNA-UFC1) promotes progression of hepatocellular carcinoma (HCC), using human tissues and cell lines.

Methods: We used microarrays to compare expression profiles of lncRNAs in HCC samples and adjacent nontumor tissues (controls) from 7 patients.

[miR-128a is up-regulated in hepatocellular carcinoma and promotes tumor cell proliferation by targeting RND3].

Objective: To investigate the expression of microRNA-128a (miR-128a) and its role in hepatocellular carcinoma (HCC).

Methods: Nineteen pairs of fresh surgical specimens of HCC and adjacent tissues were examined for miR-128a expression using qRT-PCR. A miR-128a mimics or inhibitor was transfected into HCC cells, and the cell viability was analyzed by MTT assay.

[Effect of casein kinase 2β in esophageal carcinoma and its clinical significance].

Objective: To investigate the expression of casein kinase 2β in esophageal carcinoma tissues and analyze its clinical significance.

Methods: The expression of CK2β in a tissue chip containing 60 normal esophageal mucosa and 60 colorectal cancer specimens were detected immunohistochemically. Ten human esophageal carcinoma and adjacent normal tissues were examined for the expression of CK2β protein and mRNA using Western blotting and real-time quantitative PCR, respectively.

Increased expression of OCT4 is associated with low differentiation and tumor recurrence in human hepatocellular carcinoma.

Octamer binding transcription factor 4 (OCT4), a key transcription factor required to maintain self-renewal and pluripotency of human and mouse embryonic stem cells, has been recently identified to be associated with tumorigenesis and malignant transformation of many types of cancers. This study was to determine the roles of OCT4 in HCC recurrence and their impact on the clinical outcome of HCC patients. Western blot and immunohistochemical stains were used to detect the expression of OCT4 protein in 152 HCC tissues and 40 cirrhosis tissues, as well as in 6 human HCC cell lines and normal hepatocytes.