Publications by authors named "Guoming Shi"
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.
The small G protein Arf1 has been identified as playing a selective role in supporting cancer stem cells (CSCs), making it an attractive target for cancer therapy. However, the current Arf1 inhibitors have limited translational potential due to their high toxicity and low specificity. In this study, two new potent small-molecule inhibitors of Arf1, identified as DU101 and DU102, for cancer therapy are introduced.
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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
- Intrahepatic cholangiocarcinoma (iCCA) can arise from various parts of the intrahepatic biliary tree and is classified into subtypes based on their origins, such as large duct, small duct, and cholangiolocarcinoma.
- Diagnosing these subtypes is challenging due to differences in cell structure, growth patterns, and other pathological features.
- An expert consensus has proposed nine recommendations to standardize the diagnosis of these iCCA subtypes, referring mainly to the latest World Health Organization classification.
Article Synopsis
- Primary liver cancer is a major health concern in China, with hepatocellular carcinoma accounting for 75-85% of cases, ranking as the fourth most common cancer and the second leading cause of cancer-related deaths in the country.
- The Guidelines for Diagnosis and Treatment of Primary Liver Cancer were first published in 2017 and have been updated due to new research and evidence in the field, leading to the 2022 Edition written by over 100 experts.
- The updated guidelines aim to promote evidence-based practices to enhance the 5-year survival rate of liver cancer patients in alignment with the "Health China 2030 Blueprint."
The combination of immunotherapy and molecular targeted therapy exhibits promising therapeutic efficacy in hepatocellular carcinoma (HCC), but the underlying mechanism is still unclear. Here, phosphoglycerate mutase 1 (PGAM1) is identified as a novel immunometabolic target by using a bioinformatic algorithm based on multiple HCC datasets. PGAM1 is highly expressed in HCC and associated with a poor prognosis and a poor response to immunotherapy.
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- 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.
Background: The dysregulation of exosomal microRNAs plays an important role in the progression of hepatocarcinogenesis. In this study, we investigated the therapeutic potential of synthetic exosomal miR-26a against HCC cells and explored the feasibility of tumor-derived exosomes as drug delivery vehicles.
Methods: Proliferation and migration assays were performed to examine the effects of miR-26a on HCC in vitro.
Article Synopsis
- 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
- Advanced intrahepatic cholangiocarcinoma (ICC) has poor outcomes, but a new combination therapy of toripalimab, lenvatinib, and GEMOX shows promise as a first-line treatment.
- In a study of 30 patients, the therapy resulted in an 80% objective response rate, with most experiencing either partial or complete responses, and an overall disease control rate of 93.3%.
- While manageable adverse events occurred in over half of the patients, including neutropenia and leukocytopenia, the overall survival and progression-free survival were encouraging, prompting further validation in a larger clinical trial.
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.
Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with a high prevalence in China. This study aimed to characterize the ICC tissues' bacterial metagenomics signature and explore its antitumor potential for cancer. In this study, 16S rRNA sequencing was carried out on 99 tissues to characterize the features of intratumoral microbiota, followed by single-cell RNA sequencing (scRNA-seq) and multilevel validation.
View Article and Find Full Text PDFBackground: 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: Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 10/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown.
Methods: Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled.
Purpose: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 10/L) patients undergoing elective invasive procedures.
Methods: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 10/L that increased to ≥ 20 × 10/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed.
Objective: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with a poor prognosis and limited treatment. Cisplatin with gemcitabine is used as the standard first-line chemotherapy regimen; however, there is still no robust evidence for second-line and successive treatments. Although preliminary evidence suggests a vital role of precision therapy or immunotherapy in a subset of patients, the gene alteration rate is relatively low.
View Article and Find Full Text PDFObjective: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements.
Background: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries.
Methods: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.
Background: Laparoscopic liver resection (LLR) has now been established as a safe and minimally invasive technique that is deemed feasible for treating hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, the role of LLR in treating combined hepatocellular-cholangiocarcinoma (cHCC-CC) patients has been rarely reported. This study aimed to assess the efficacy of LLR when compared with open liver resection (OLR) procedure for patients with cHCC-CC.
View Article and Find Full Text PDFBackground: Tumor-associated macrophages (TAMs), which form a large part of the tumor microenvironment, are normally regulated by metabolic reprogramming. However, the potential mechanisms of the immune-metabolism interaction between hepatocellular carcinoma (HCC) cells and TAMs remain unclear.
Methods: The candidate long non-coding RNAs (lncRNAs) were screened by Smart-seq based scRNA-seq method and then validated by qPCR.
Background And Aims: Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding and few effective therapeutic approaches. We aimed at providing a proteogenomic CCA characterization to inform biological processes and treatment vulnerabilities.
Approach And Results: Integrative genomic analysis with functional validation uncovered biological perturbations downstream of driver events including DPCR1 , RBM47 mutations, SH3BGRL2 copy number alterations, and FGFR2 fusions in CCA.
Background: Most intrahepatic cholangiocarcinomas (ICCs) are diagnosed at advanced stage with an extremely poor prognosis. For these patients, combining targeted therapies and immunotherapy may have a promising therapeutic effect, and current Response Evaluation Criteria in Solid Tumors (RECIST) criteria have limited applicability.
Purpose: To investigate the associations between pretreatment MRI features and the efficacy of combined targeted-immunotherapy by estimating the risk of early progression (EP) in unresectable ICC, with special emphasis on diffusion-weighted imaging.
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.