Olaparib enhances radiation-induced systemic anti-tumor effects via activating STING-chemokine signaling in hepatocellular carcinoma.

Although Poly (ADP-ribose) polymerase (PARP) inhibitors have been clinically approved for cancers with BRCA mutations and are known to augment radiotherapy responses, their roles in promoting the abscopal effect and mediating immunotherapy in BRCA-proficient hepatocellular carcinoma (HCC) remain underexplored. Our study elucidates that olaparib enhances the radio-sensitivity of HCC cells. Coadministration of olaparib and irradiation induces significant DNA damage by generating double-strand breaks (DSBs), as revealed both in vitro and in immune-deficient mice.

miR-146a-5p Alleviates Radiation-Induced Liver Fibrosis by Regulating PTPRA-SRC Signaling in Mice.

Patients with hepatobiliary tumors who accept radiotherapy are at risk for radiation-induced liver fibrosis. MicroRNAs (miRNAs) have been implicated in the pathogenesis of radiation-induced liver damage and possess potential as novel biomarkers and therapeutic targets. However, the role of miR-146a-5p in radiation-induced liver fibrosis is less well understood.

METTL3-Mediated STING Upregulation and Activation in Kupffer Cells Contribute to Radiation-Induced Liver Disease via Pyroptosis.

Purpose: Radiation therapy is a vital adjuvant treatment for liver cancer, although the challenge of radiation-induced liver diseases (RILDs) limits its implementation. Kupffer cells (KCs) are a crucial cell population of the hepatic immune system, and their biologic function can be modulated by multiple epigenetic RNA modifications, including N-methyladenosine (mA) methylation. However, the mechanism for mA methylation in KC-induced inflammatory responses in RILD remains unclear.

Radiation Therapy Promotes Hepatocellular Carcinoma Immune Cloaking via PD-L1 Upregulation Induced by cGAS-STING Activation.

Purpose: Radiation therapy (RT) is one of the main treatments for patients with unresectable hepatocellular carcinoma (HCC). Emerging evidence indicates that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon gene (STING) pathway is crucial in RT-induced antitumor immune responses. Here, we discovered that activation of the cancer cell-intrinsic cGAS-STING pathway mediated immune cloaking after RT-induced DNA damage.

Exploiting Canonical TGFβ Signaling in Cancer Treatment.

TGFβ is a pleiotropic cytokine that plays critical roles to define cancer cell phenotypes, construct the tumor microenvironment, and suppress antitumor immune responses. As such, TGFβ is a lynchpin for integrating cancer cell intrinsic pathways and communication among host cells in the tumor and beyond that together affect responses to genotoxic, targeted, and immune therapy. Despite decades of preclinical and clinical studies, evidence of clinical benefit from targeting TGFβ in cancer remains elusive.

Network-Based Expression Analyses and Experimental Verifications Reveal the Involvement of STUB1 in Acute Kidney Injury.

Acute kidney injury (AKI) is a severe and frequently observed condition associated with high morbidity and mortality. The molecular mechanisms underlying AKI have not been elucidated due to the complexity of the pathophysiological processes. Thus, we investigated the key biological molecules contributing to AKI based on the transcriptome profile.

ALKBH5-Modified HMGB1-STING Activation Contributes to Radiation Induced Liver Disease via Innate Immune Response.

Purpose: Radiation therapy, which is vital for the treatment of primary liver cancer, comes with unavoidable liver injury, which limits its implementation. N6-methyladenosine (m6A) methylation is involved in many molecular functions. However, its role in radiation-induced liver diseases (RILD) remains unknown.

Bastnäsite nanoparticles in carbonatite-syenite-hosted REE deposit： implication for La and Ce migration and bastnäsite growth.

High-resolution transmission electron microscopy observations of bastnäsite from the Maoniuping rare earth element (REE) deposit at Panxi, SW China, revealed the presence of nanoparticles in the surface of bastnäsite crystal. The nanoparticles are identified as the bastnäsite nanocrystals, with 5-30 nm in length, by energy-dispersive spectrometry and fast fourier transform patterns. This represents the first observation of bastnäsite nanoparticle in nature, confirming a new form of migration and precipitation of La and Ce in the hydrothermal fluids.

A Nomogram for Predicting Cancer-Specific Survival of Patients with Gastrointestinal Stromal Tumors.

BACKGROUND The aim of this study was to construct a nomogram to predict the prognosis of patients with gastrointestinal stromal tumor (GIST). MATERIAL AND METHODS We enrolled 4086 GIST patients listed in the SEER database from 1998 to 2015. They were separated to 2 groups: an experimental group (n=2862) and a verification group (n=1224).

DNA sensing and associated type 1 interferon signaling contributes to progression of radiation-induced liver injury.

Liver damage upon exposure to ionizing radiation (IR), whether accidental or therapeutic, can contribute to liver dysfunction. Currently, radiotherapy (RT) is used for various cancers including hepatocellular carcinoma (HCC); however, the treatment dose is limited by radiation-induced liver disease (RILD) with a high mortality rate. Furthermore, the precise molecular mechanisms of RILD remain poorly understood.

Pre/Post-Treatment Dynamic of Inflammatory Markers Has Prognostic Value in Patients with Small Hepatocellular Carcinoma Managed by Stereotactic Body Radiation Therapy.

Purpose: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT).

Patients And Methods: Sixty patients who received SBRT were retrospectively reviewed.

Profiles of immune infiltration in lung adenocarcinoma and their clinical significant: A gene-expression-based retrospective study.

Lung cancer is one of the fatal tumors. The tumor microenvironment plays a key role in regulating tumor progression. To figure out the role of tumor microenvironment in lung adenocarcinoma (LUAD), ESTIMATE algorithm was used to evaluate the immune scores in LUAD.

Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR-146a-5p.

The role of circular RNA (circRNA) in radiation-induced liver disease (RILD) remains largely unknown. In this study, Ras-related C3 botulinum toxin substrate 1 (RAC1) was elevated in irradiated human hepatic stellate cell (HSC) line LX2, the important effector cell mediating RILD. Overexpression of RAC1 promotes cell proliferation, proinflammatory cytokines production, and α-smooth muscle actin expression, which were blocked by microRNA (miR)-146a-5p mimics.

MicroRNA-146a-5p Attenuates Fibrosis-related Molecules in Irradiated and TGF-beta1-Treated Human Hepatic Stellate Cells by Regulating PTPRA-SRC Signaling.

MicroRNAs (miRNAs) have been shown to play a pivotal role in the pathogenesis and maintenance of liver fibrosis by altering expression of their downstream target genes. However, their role in radiation-induced liver fibrosis has not been assessed in detail. Here, we investigated the role of miR-146a-5p and the target gene in regulation of fibrosis-related markers in the human hepatic stellate cell line LX2.

Association Between Circulating Lymphocyte Populations and Outcome After Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma.

Radiation-induced lymphopenia has a tangible impact on overall survival (OS) in multiple solid tumors. We investigated the association between circulating lymphocyte populations (CLPs) before and after stereotactic body radiation therapy (SBRT) and OS in patients with hepatocellular carcinoma (HCC). Seventy-eight HCC patients treated with SBRT between January 2013 and June 2017 were retrospectively analyzed.

The molecular mechanism of LncRNA34a-mediated regulation of bone metastasis in hepatocellular carcinoma.

Background: Bone metastasis (BM) has long been recognized as a major threat to the quality of life of hepatocellular cancer (HCC) patients. While LncRNA34a (Lnc34a) has been shown to regulate colon cancer stem cell asymmetric division, its effect on HCC BM remains unknown.

Methods: In situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of Lnc34a in HCC tissues and cell lines.

Label‑free quantitative proteomics and bioinformatics analyses of alcoholic liver disease in a chronic and binge mouse model.

As a significant cause of mortality and morbidity, alcoholic liver disease (ALD) has been widely investigated. However, little is known about the underlying metabolic mechanisms involved in the complicated pathological processes of ALD. The present study used label‑free quantitative proteomics and bioinformatics analyses to investigate the differentially expressed proteins (DEPs) and their functions in the livers of alcohol‑feed (AF) and control pair‑feed (PF) mice.

circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma.

Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124.

CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the proliferation of PDAC cells.