Publications by authors named "Ai-Wu Ke"
Article Synopsis
- Single-cell technology offers a more comprehensive view of tumors by analyzing both tumor cells and their surrounding microenvironments, potentially improving diagnosis compared to traditional methods that focus solely on pathology.
- Despite its advantages, single-cell RNA sequencing (scRNA-seq) faces significant issues, including complex data structures and low signal clarity, which hinder its diagnostic use.
- The authors introduce a graph neural network framework designed for diagnosing primary liver tumors by leveraging scRNA-seq data and intercellular communication networks, demonstrating accurate differentiation between malignant and benign tumors and validating their findings with public datasets.
Article Synopsis
- * Radiotherapy (RT) not only damages DNA in cancer cells but also activates inflammatory signaling pathways that can reshape the immune environment, enhancing tumor control and potentially triggering immune responses in distant tumors (abscopal effects).
- * The review highlights the importance of understanding GI in cancer biology, suggesting that combining RT with immunotherapy may lead to better treatment strategies and improved patient outcomes by harnessing systemic anti-tumor immunity.
Lenvatinib is the most common multitarget receptor tyrosine kinase inhibitor for the treatment of advanced hepatocellular carcinoma (HCC). Acquired resistance to lenvatinib is one of the major factors leading to the failure of HCC treatment, but the underlying mechanism has not been fully characterized. We established lenvatinib-resistant cell lines, cell-derived xenografts (CDXs) and patient-derived xenografts (PDXs) and obtained lenvatinib-resistant HCC tumor tissues for further study.
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- Intratumoral immune status plays a crucial role in how patients with intrahepatic cholangiocarcinoma respond to therapy, especially with a combination of gemcitabine, oxaliplatin, lenvatinib, and anti-PD1 antibody.
- High levels of certain CD8 T-cell markers (GZMB and proliferating CD8) and low levels of Macro CD5L predict better therapeutic responses, while shifts in T-cell markers indicate varying response levels.
- The study also suggests that using anti-CTLA4 antibody can counteract therapy resistance caused by immune exhaustion, paving the way for more effective cancer treatments based on immune profiling.
Article Synopsis
- The tumor microenvironment is complex and includes tumor-associated macrophages (TAMs), which can be influenced by tumor cells to create an environment that supports tumor growth.
- This study found that liver cancer (HCC) cells cause macrophages to change into a M2-like phenotype, which is associated with promoting cancer, and that this change is linked to the role of autophagy in macrophage behavior.
- Inhibiting autophagy in macrophages leads to M2 polarization through a specific mechanism involving the NF-κB pathway, highlighting a potential target for cancer treatment by disrupting this polarization process.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with few effective treatment options. Lenvatinib is the first-line therapy for HCC but has only limited clinical benefit. Here, we explored the role and mechanism of the WD repeat domain 4 (WDR4) in lenvatinib resistance to improve clinical benefit.
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- Evading the immune system is a key feature of cancer, particularly in the development of hepatocellular carcinoma (HCC), and understanding this process is crucial for finding new treatments.
- The study identifies miR-93-5p as a significant oncogene involved in HCC progression and immune evasion, as it disrupts tumor suppressors and affects immune cell function.
- Blocking GAL-9, which is linked to high levels of miR-93-5p, shows promise as a new immunotherapeutic strategy to counteract HCC and improve patient outcomes.
Article Synopsis
- The study investigates the role of autophagy in macrophages within the tumor microenvironment of hepatocellular carcinoma (HCC), finding reduced autophagy linked to worse patient outcomes and increased metastasis.
- Researchers identified that HCC triggers decreased autophagy in macrophages by activating mTOR, which in turn promotes cancer progression through mechanisms involving the NLRP3 inflammasome and IL-1β release.
- Targeting the signaling pathways related to IL-1β showed potential as a therapeutic strategy, indicating that disrupting the feedback loop between autophagy inhibition and macrophage recruitment could help treat HCC more effectively.
Article Synopsis
- * Lower levels of 5-hydroxymethylcytosine (5-hmC) in HCC tissues are associated with worse cancer characteristics and resistance to chemotherapy after liver transplantation.
- * The enzyme TET2 regulates 5-hmC levels, and its reduction leads to chemotherapy resistance via inhibition of PCAF and hyperactivation of AKT signaling, making it a potential target for improving treatment outcomes.
Background: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis.
Methods: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort.
Background: Kinase suppressor of Ras 2 (KSR2) is a regulator of MAPK signaling that is overactivated in most hepatocellular carcinoma (HCC). We sought to determine the role of KSR2 in HCC pathogenesis.
Methods: We tested the level of KSR2 in HCC tissues and cell lines by tissue microarray, qPCR, and western blotting.
Background: While the correlation between PD-L1 expression and KRAS mutation has been previously reported in other solid tumors such as non-small cell lung cancer (NSCLC), whether PD-L1 can be modulated by ERK signaling downstream of KRAS in intrahepatic cholangiocarcinoma (iCCA) and the underlying molecular regulatory mechanism remain unclear.
Methods: The expression of ERK, p-ERK, PD-L1 and autophagy markers following KRAS knockdown or Ras/Raf/MEK/ERK signaling inhibitors treatment was examined in two human iCCA cell lines (HuCCT1 and RBE) using western blotting and immunofluorescence. Both pharmacological autophagy inhibitors and short-interfering RNA against ATG7 were applied to inhibit autophagy.
Background & Aims: Despite remarkable advances in treatment, most patients with hepatocellular carcinoma (HCC) respond poorly to anti-programmed cell death 1 (anti-PD1) therapy. A deeper insight into the tolerance mechanism of HCC against this therapy is urgently needed.
Methods: We performed next-generation sequencing, multiplex immunofluorescence, and dual-color immunohistochemistry and constructed an orthotopic HCC xenograft tumor model to identify the key gene associated with anti-PD1 tolerance.
Article Synopsis
- The CRISPR system provides a way for prokaryotes to fight off viruses and plasmids, leading to the creation of the CRISPR/Cas9 genome editing tool, known for its precision and efficiency in genetic manipulation.
- This technology has revolutionized cancer research by helping scientists study cancer-related genes, create animal models, and identify drug targets, thereby deepening our understanding of cancer genomics.
- The review covers the principles of CRISPR/Cas9, new editing methods, advancements in cancer-related screening, delivery systems for the technology, and its potential to improve adoptive T cell therapy and minimize side effects.
Background: Immune checkpoint blockade resistance narrows the efficacy of cancer immunotherapies, but the underlying mechanism remains elusive. Delineating the inherent mechanisms of anti-PD1 resistance is important to improve outcome of patients with advanced HCC.
Method: The level of cricTMEM181 was measured in HCC patients with anti-PD1 therapy by RNA sequencing and then confirmed by qPCR and Sanger sequencing.
Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed.
View Article and Find Full Text PDFBackground: Cirrhosis is a recognized risk factor for developing hepatocellular carcinoma (HCC). Few studies have reported the expression profile of circRNAs in HCC samples compared to paratumour dysplastic nodule (DN) samples.
Methods: The Arraystar Human circRNA Array combined with laser capture microdissection (LCM) was used to analyse the expression profile of circRNAs in HCC samples compared to paratumour DN samples.
Background: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC.
Materials And Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC.
Objective: Tumour pathology contains rich information, including tissue structure and cell morphology, that reflects disease progression and patient survival. However, phenotypic information is subtle and complex, making the discovery of prognostic indicators from pathological images challenging.
Design: An interpretable, weakly supervised deep learning framework incorporating prior knowledge was proposed to analyse hepatocellular carcinoma (HCC) and explore new prognostic phenotypes on pathological whole-slide images (WSIs) from the Zhongshan cohort of 1125 HCC patients (2451 WSIs) and TCGA cohort of 320 HCC patients (320 WSIs).
Article Synopsis
- Natural killer (NK) cells are important for fighting tumors, but their dysfunction is observed in hepatocellular carcinoma (HCC), which is not fully understood.
- The study found that the circular RNA circUHRF1 is expressed at higher levels in HCC tissues and correlates with poor prognosis and NK cell dysfunction by reducing their ability to secrete key immune signals.
- CircUHRF1 also contributes to NK cell dysfunction by promoting TIM-3 expression through miR-449c-5p degradation, potentially leading to resistance against immunotherapy in HCC patients.
Background: Amplification of chromosome 7q21-7q31 is associated with tumor recurrence and multidrug resistance, and several genes in this region are powerful drivers of hepatocellular carcinoma (HCC). We aimed to investigate the key circular RNAs (circRNAs) in this region that regulate the initiation and development of HCC.
Methods: We used qRT-PCR to assess the expression of 43 putative circRNAs in this chromosomal region in human HCC and matched nontumor tissues.
Dysregulation of microRNA (miRNA) is a frequent event in hepatocellular carcinoma (HCC), but little is known whether it is a bystander or an actual player on residual HCC metastasis during liver microenvironment remodeling initiated by hepatectomy. The differently expressed miRNAs and mRNAs were identified from RNA-seq data. Western blot, qRT-PCR, fluorescence hybridization, immunofluorescence and immunohistochemical were used to detect the expression of miRNA and mRNA in cell lines and patient tissues.
View Article and Find Full Text PDFThere are some controversies about the involvement of microRNA (miR)-19a-3p in hepatocellular carcinoma (HCC) biology, even though many studies have shown that it plays an important role in cancer. In this study, we found that miR-19a-3p is usually overexpressed in HCC tissues compared with corresponding peritumorous tissues, and its expression was associated with tumor size and poor overall survival. MiR-19a-3p promoted cell proliferation significantly, and more cells were found in the S phase.
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