Micropeptide hSPAR regulates glutamine levels and suppresses mammary tumor growth via a TRIM21-P27KIP1-mTOR axis.

mTOR plays a pivotal role in cancer growth control upon amino acid response. Recently, CDK inhibitor P27KIP1 has been reported as a noncanonical inhibitor of mTOR signaling in MEFs, via unclear mechanisms. Here, we find that P27KIP1 degradation via E3 ligase TRIM21 is inhibited by human micropeptide hSPAR through its C-terminus (hSPAR-C), causing P27KIP1's cytoplasmic accumulation in breast cancer cells.

VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8T cells function in the HCC microenvironment.

CD8T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8T cells suppression in hepatocellular carcinoma (HCC).

Laennec approach for anatomical liver resection assisted by laparoscopy or robotics: a multicenter cohort study.

Introduction: Laennec's capsule serves as a critical anatomical landmark in anatomical liver resection. Despite its potential, a lack of large-scale prospective studies limits the widespread use of the Laennec approach for minimally invasive hepatectomy. This multicenter cohort study aimed to compare the outcomes of the traditional and Laennec approaches in minimally invasive anatomical hepatectomy across multiple centers in China.

Phase 2 study of serplulimab with the bevacizumab biosimilar HLX04 in the first-line treatment of advanced hepatocellular carcinoma.

Introduction: This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma.

Methods: This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line).

Chinese expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2024 edition).

Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits.

Alpha-fetoprotein combined with initial tumor shape irregularity in predicting the survival of patients with advanced hepatocellular carcinoma treated with immune-checkpoint inhibitors: a retrospective multi-center cohort study.

Background: Immune checkpoint inhibitors (ICIs) are playing a significant role in the treatment of hepatocellular carcinoma (HCC). This study aims to explore the prognostic value of alpha-fetoprotein (AFP) and initial tumor shape irregularity in patients treated with ICIs.

Methods: In this retrospective, multi-center study, 296 HCC patients were randomly divided into the training set and the validation set in a 3:2 ratio.

A STT3A-dependent PD-L1 glycosylation modification mediated by GMPS drives tumor immune evasion in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor characterized by rapid progression. To explore the regulatory mechanism of rapid tumor growth and metastasis, we conducted proteomic and scRNA-Seq analyses on advanced HCC tissues and identified a significant molecule, guanine monophosphate synthase (GMPS), closely associated with the immune evasion in HCC. We analyzed the immune microenvironment characteristics remodeled by GMPS using scRNA-Seq and found GMPS induced tumor immune evasion in HCC by impairing the tumor-killing function of CD8  T cells.

Chinese guidelines for minimally invasive donor hepatectomy in living donor liver transplantation (2024 edition).

Background: Minimally invasive surgeries are increasingly central to modern medicine, particularly in liver transplantation. These techniques, which offer reduced trauma, precise operations, minimal bleeding, and swift recovery, are, however, unevenly adopted across China. Only a limited number of centers routinely perform minimally invasive donor hepatectomies, indicating a significant imbalance in the development and application of these advanced procedures.

Comparison of 2 Different Types of Arterial and Biliary Anastomoses While Preserving the Gastroduodenal Artery: A Retrospective Study.

Objective: Here we investigated 2 different arterial reconstruction procedures with preservation of the gastroduodenal artery (GDA) in orthotopic liver transplantation (OLT).

Methods: A retrospective cohort study was conducted. The clinicopathological data of 40 pairs of donors and recipients who underwent OLT from May 2018 to August 2023 were analyzed.

PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression.

Internal tandem duplication (ITD) in the FMS-like receptor tyrosine kinase-3 (FLT3) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with poor prognosis. FLT3-ITD mutations result in endoplasmic reticulum (ER) retention and constitutive autophosphorylation of FLT3. The PR/SET domain 16 (PRDM16) is highly expressed in FLT3-ITD+ AML patients, suggesting it might play a role in leukemogenesis.

Exploring the Interplay of Diet, Obesity, Immune Function, and Cancer.

This commentary provides an in-depth exploration of the intricate relationships among diet, obesity, immune function, and cancer, highlighting the potential role of dietary interventions as complementary therapies in cancer treatment. Multiple analyses underscore the importance of personalized dietary strategies in cancer management and identify opportunities for further research in this evolving field.

Exploring the role of the immune microenvironment in hepatocellular carcinoma: Implications for immunotherapy and drug resistance.

Hepatocellular carcinoma (HCC), the most common type of liver tumor, is a leading cause of cancer-related deaths, and the incidence of liver cancer is still increasing worldwide. Curative hepatectomy or liver transplantation is only indicated for a small population of patients with early-stage HCC. However, most patients with HCC are not candidates for radical resection due to disease progression, leading to the choice of the conventional tyrosine kinase inhibitor drug sorafenib as first-line treatment.

Diagnosis and Treatment of Hepatic Hematoma After Liver Transplantation in a Timely Manner.

Objective: Hematomas of the liver graft, that is, postintervention, subcapsular or intrahepatic are rare yet potentially fatal complications following liver transplantation (LT), necessitating immediate diagnosis and management to avert devastating outcomes. This study was aimed to introduce our approach to manage graft hematoma subsequent to LT.

Methods: Among 131 orthotopic liver transplantations (OLT) conducted at our institution between January 2017 and May 2023, 3 cases of intrahepatic (n = 2) and extrahepatic (n = 1) hematoma were confirmed through computed tomography (CT) within 10 days after LT.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

Background: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients.

Methods: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients.

Impact of major hepatectomy on recurrence after resection of hepatocellular carcinoma at CNLC Ib stage: a propensity score matching study.

Objective: Patients with hepatocellular carcinoma (HCC) who undergo curative hepatectomy may experience varying remnant liver volumes. Our study aimed to evaluate whether the extent of liver resection has an effect on postoperative recurrence in HCC patients at China Liver Cancer Staging (CNLC) Ib stage.

Methods: A retrospective analysis was conducted on 197 patients who underwent hepatectomy for a solitary HCC lesion measuring ≥5 cm (CNLC Ιb stage) between January 2019 and June 2022.

Acetylation-dependent regulation of core spliceosome modulates hepatocellular carcinoma cassette exons and sensitivity to PARP inhibitors.

Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets.

Adjuvant donafenib for hepatocellular carcinoma patients at high-risk of recurrence after radical resection: a real-world experience.

Background: Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported.

Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development.

Patient-derived organoids (PDOs) have emerged as a promising platform for clinical and translational studies. A strong correlation exists between clinical outcomes and the use of PDOs to predict the efficacy of chemotherapy and/or radiotherapy. To standardize interpretation and enhance scientific communication in the field of cancer precision medicine, we revisit the concept of PDO-based drug sensitivity testing (DST).

IFRD1 promotes tumor cells "low-cost" survival under glutamine starvation via inhibiting histone H1.0 nucleophagy.

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner.

Surgical treatment improves overall survival of hepatocellular carcinoma with extrahepatic metastases after conversion therapy: a multicenter retrospective study.

Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor.