NCOA3 impairs the efficacy of anti-PD-L1 therapy via HSP90α/EZH2/CXCL9 axis in colon cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized colon cancer treatment, but their efficacy is largely restricted by the limited presence of CD8 cytotoxic T lymphocytes (CTLs). However, the specific genetic alterations that impact the CD8 CTL infiltration in colon cancer remain poorly understood. Here, we analyzed clinical and multi-omics data from the Memorial Sloan-Kettering Cancer Center (MSKCC) ICIs-treated and The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohorts to screen the key mutations that may influence the efficacy of immunotherapy.

Tumor derived exosomal ENTPD2 impair CD8 T cell function in colon cancer through ATP-adenosine metabolism reprogramming.

Background: Extracellular ATP-AMP-adenosine metabolism plays a pivotal role in modulating tumor immune responses. Previous studies have shown that the conversion of ATP to AMP is primarily catalysed by Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39), a widely studied ATPase, which is expressed in tumor-associated immune cells. However, the function of ATPases derived from tumor cells themselves remains poorly understood.

HIF-1α Mediates Immunosuppression and Chemoresistance in Colorectal Cancer by Inhibiting CXCL9, -10 and -11.

Uncertainty exists regarding the mechanisms by which hypoxia-inducible factors (HIFs) control CD8T-cell migration into tumor microenvironments. Here, we found that HIF-1α knockdown or overexpression resulted in increased or decreased CXCL9, -10, and -11 expression in vitro, respectively. Gene Set Variation Analysis revealed that elevated HIF-1α levels correlated with a poor prognosis, severe pathological stage, and an absence of CD8 T cells in the tumor microenvironment in colorectal cancer (CRC) patients.

Knockdown LIMP2 inhibits colorectal cancer cells migration, invasion, and metastasis.

Colorectal cancer (CRC) is a common malignancy worldwide nowadays and liver metastasis is the primary cause of death in patients with CRC. Although lysosomal integral membrane protein 2 (LIMP2) has been reported to play important roles in gastric cancer and prostate cancer, its role in CRC remains unclear. The aim of this study was to investigate the function of LIMP2 in CRC invasion and migration, along with the potential underlying molecular mechanisms.

Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer.

Apolipoprotein E (apoE) has previously been reported to play vital roles in tumor progression. However, the impact of apoE on colorectal cancer (CRC) metastasis remains largely unexplored. This study aimed to investigate the role of apoE in CRC metastasis and to identify the transcription factor and receptor of apoE involved in regulation of CRC metastasis.

Evacetrapib Elicits Antitumor Effects on Colorectal Cancer by Inhibiting the Wnt/β-Catenin Signaling Pathway and Activating the JNK Signaling Pathway.

Despite advances in colorectal cancer (CRC) treatment, most advanced CRC patients who experience disease progression after chemotherapy, targeted therapy, and immunotherapy face a situation in which there is no available medicine. Thus, new therapeutic drugs for CRC are urgently needed. Studies have shown that cholesteryl ester transfer protein (CETP) has a vital role in tumor development and is a possible target for CRC therapy.

Potential roles of serum ATPase and AMPase in predicting diagnosis of colorectal cancer patients.

Colorectal cancer (CRC) is a common gastrointestinal cancer with high incidence and mortality rates. CRC may be associated with regulation of circulating nucleotides. This study aimed to evaluate the serum levels of nucleotide-metabolizing enzymes (ATPase and AMPase) in patients with CRC and to explore the clinical diagnostic value of these enzymes.

Pyrimethamine inhibits cell growth by inducing cell senescence and boosting CD8 T-cell mediated cytotoxicity in colorectal cancer.

Background: The emergence of nonresponse or resistance to traditional chemotherapeutic agents is one of the main challenges of colorectal cancer (CRC) therapies. Thus, novel therapeutic drugs that can improve the clinical outcomes of CRC patients are urgently needed. The purpose of this study was to investigate the effects and mechanisms of pyrimethamine in CRC.

The Genotype (A to H) Dependent N-terminal Sequence of HBV Large Surface Protein Affects Viral Replication, Secretion and Infectivity.

Genetic variability has significant impacts on biological characteristics and pathogenicity of hepatitis B virus (HBV), in which the N-terminal sequence of the presurface 1 (preS1) region of HBV large surface protein (LHBs) displays genotype (GT) dependent genetic heterogeneity. However, the influence of this heterogeneity on its biological roles is largely unknown. By analyzing 6560 full-length genome sequences of GTA-GTH downloaded from HBVdb database, the preS1 N-terminal sequences were divided into four representative types, namely C-type (representative of GTA, GTB, and GTC), H-type (GTF and GTH), E-type (GTE and GTG), and D-type (GTD), respectively.

A novel cell culture model reveals the viral interference during hepatitis B and C virus coinfection.

Coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may result in severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that HBV replication is suppressed by replicating HCV and often rebounds after treatment with drugs against HCV. Thus, a highly efficient cell culture system permissive for HBV/HCV would facilitate investigation on the interaction and pathogenesis after coinfection.

The modulation of HBsAg level by sI126T is affected by additional amino acid substitutions in the S region of HBV.

The hepatitis B surface antigen (HBsAg) is a vital serum marker for hepatitis B virus (HBV) infection. Amino acid (AA) substitutions in small hepatitis B surface protein (SHBs) are known to affect HBsAg level. However, how the genetic backbones of SHBs sequences would affect the roles of a specific AA substitution on HBsAg level remains unclear.

The Effect of the Hepatitis B Virus Surface Protein Truncated sC69 Mutation on Viral Infectivity and the Host Innate Immune Response.

Viruses could rapidly diversify into variants, which has long been known to facilitate viral adaption in the host. Recent studies showed that cooperation among variants and wild-type (WT) also increased viral fitness. Here, a mutant of sC69 in small hepatitis B surface protein (SHBs) that resulted in premature stop was investigated and the frequency of sC69 was 4.

Characteristics of HBV infection in 705 HIV-infected patients under lamivudine-based antiretroviral treatment from three regions in China.

Purpose: This study aimed to investigate the HIV and hepatitis B virus (HBV) co-infection in three HIV high endemic areas with different modes of HIV transmission and explore the HBV nucleos(t)ide analogue resistance (NUCr) substitutions in this cohort receiving antiretroviral therapy (ART).

Patients And Methods: The enrolled 705 HIV-infected patients were from three different regions in China and received lamivudine-based ART for at least 1 year. After screening for hepatitis B surface antigen (HBsAg), the hepatitis B e antigen (HBeAg), and antibody against hepatitis B core antigen (anti-HBc and anti-HBc IgM), HBV DNA in plasma of patients positive for HBsAg was tested.