Inhibition of HIF-prolyl hydroxylase promotes renal tubule regeneration via the reprogramming of renal proximal tubular cells.

The ability of the mammalian kidney to repair or regenerate after acute kidney injury (AKI) is very limited. The maladaptive repair of AKI promotes progression to chronic kidney disease (CKD). Therefore, new strategies to promote the repair/regeneration of injured renal tubules after AKI are urgently needed.

Prediction model establishment of prognosis factors for acute myeloid leukemia based on the SEER database.

Acute myeloid leukemia (AML) with t (9;11) (p22; q23) presents as a varied hematological malignancy. The t (9;11) (p22; q23) translocation is the most common among 11q23/KMT2A rearrangements in AML. This research aimed to develop a nomogram for precise prediction of overall survival (OS) and cancer-specific survival (CSS) in AML with the t (9;11) (p22; q23) translocation.

CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability.

The integrated analysis of histone modifier enzymes in solid tumors, especially in esophageal squamous cell carcinoma (ESCC), is still inadequate. Here, we investigate the expression levels of histone modifier enzymes in ESCC tissues. Notably, KAT8 (lysine acetyltransferase 8) is identified as a prognostic and therapeutic biomarker in ESCC.

SLC35C2 promotes stemness and progression in hepatocellular carcinoma by activating lipogenesis.

Metabolic reprogramming plays a critical role in in tumorigenesis and progression, including hepatocellular carcinoma (HCC). The Solute Carriers (SLCs) family is responsible for the transport of a range of nutrients and has been linked to various cancers. Cancer stem cells (CSC) are a contributing factor to the recurrence and metastasis of HCC.

PLK1 inhibition impairs erythroid differentiation.

Polo-like kinase 1 (PLK1), a key regulator of the G2/M phase in mitosis, is frequently overexpressed in numerous tumors. Although PLK1 inhibitors have emerged as promising therapeutic agents for cancer, their use has been linked to significant anemia in a subset of patients, yet the underlying mechanisms remain poorly understood. In this study, we utilized an human umbilical cord blood-derived CD34 cell-based erythroid differentiation system, alongside a murine model, to investigate the impact of PLK1 inhibitors on erythropoiesis.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

Molecular glue degrader for tumor treatment.

Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target "undruggable" proteins. This marks a revolutionary advancement in the landscape of small molecule drugs.

Role of COL5A1 in lung squamous cell Carcinoma: Prognostic Implications and therapeutic potential.

Background: Lung squamous cell carcinoma (LUSC) is a significant health concern, characterized by a lack of specific therapies and limited treatment options for patients in advanced stages. This study aims to identify key molecules of prognostic importance in LUSC and provide an experimental foundation for their potential therapeutic applications.

Methods: Immune-related transcriptome expression analysis was performed on LUSC samples using the NanoString digital gene analysis system to develop a prognostic transcriptomic signature.

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).

Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study.

This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m).

Targeting the ALKBH5-NLRP3 positive feedback loop alleviates cardiomyocyte pyroptosis after myocardial infarction.

Several studies have associated the epitranscriptomic RNA modification of N6-methyladenosine (mA) with cardiovascular diseases; however, how mA modification affects cardiomyocyte pyroptosis after myocardial infarction (MI) remains unknown. Here, we showed that AlkB homolog 5 (ALKBH5), an mA demethylase, is crucial in cardiomyocyte pyroptosis after MI. We used MI rat and mouse models, a cell hypoxia model of rat primary cardiomyocytes (RCMs), and rat embryonic ventricle cell line (H9c2) to explore the functional role of mA modification and ALKBH5 in the heart and cardiomyocytes.

Dual inhibition of LAG-3 and PD-1 with IBI110 and sintilimab in advanced solid tumors: the first-in-human phase Ia/Ib study.

Background: Co-inhibition of immune checkpoints lymphocyte-activation gene 3 (LAG-3) and PD-1 is believed to enhance cancer immunotherapy through synergistic effects. Herein, we evaluate the safety and efficacy of IBI110 (anti-LAG-3 antibody) with sintilimab (an anti-PD-1 antibody) in Chinese patients with advanced solid tumors.

Methods: In this open-label phase I study, phase Ia dose escalation of IBI110 monotherapy and phase Ib combination dose escalation of IBI110 plus sintilimab were conducted in patients with advanced solid tumors.

Immunochemotherapy plus radiotherapy versus immunochemotherapy alone as first-line treatment for treatment-naïve, advanced esophageal squamous cell carcinoma (AEC-ICR-1st): A multi-center cohort study.

Immunochemotherapy is Currently the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). However, its prognosis remains unsatisfactory. We aimed to evaluate the efficacy and safety of immunochemotherapy plus radiotherapy (ICR) compared with immunochemotherapy (IC) alone as a first-line treatment for advanced ESCC.

Anlotinib enhances the pro-apoptotic effect of APG-115 on acute myeloid leukemia cell lines by inhibiting the P13K/AKT signaling pathway.

Background: APG-115 is a novel small-molecule selective inhibitor that destabilizes the p53-MDM2 complex and activates p53-mediated apoptosis in tumor cells. Anlotinib inhibits tumor angiogenesis and promotes apoptosis. In this study, we investigated the apoptotic effect and potential mechanism of APG-115 and anlotinib combination on AML cell lines with different p53 backgrounds.

Machine learning-based prediction of duodenal stump leakage following laparoscopic gastrectomy for gastric cancer.

Background: Duodenal stump leakage is one of the most critical complications following gastrectomy surgery, with a high mortality rate. The present study aimed to establish a predictive model based on machine learning for forecasting the occurrence of duodenal stump leakage in patients who underwent laparoscopic gastrectomy for gastric cancer.

Materials And Methods: The present study included the data of 4,070 patients with gastric adenocarcinoma who received laparoscopic gastrectomy.

Detection of a novel DNA methylation marker panel for esophageal cancer diagnosis using circulating tumor DNA.

Background: Esophageal cancer (ECa) is one of the most deadly cancers, with increasing incidence worldwide and poor prognosis. While endoscopy is recommended for the detection of ECa in high-risk individuals, it is not suitable for large-scale screening due to its invasiveness and inconvenience.

Methods: In this study, a novel gene methylation panel was developed for a blood-based test, and its diagnostic efficacy was evaluated using a cohort of 304 participants (203 cases, 101 controls).

AYVM to AYMM transition on HER2 exon 20 insertion induces TKI resistance in NSCLC.

Pyrotinib, a novel pan-HER tyrosine kinase inhibitor, has demonstrated substantial anti-tumor activity in non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. However, the inevitable resistance to pyrotinib necessitates an in-depth understanding of the underlying mechanisms. In this study, potential resistance-associated mutations were identified through genomic sequencing of clinically paired samples and were validated using in vitro and in vivo models.

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.

Omitting elective neck dissection in cT1/2N0 oral squamous cell carcinoma with sentinel lymph node metastasis: A prospective study.

Objective: To examine the distribution of non-sentinel lymph nodes (SLNs) and to determine the feasibility of omitting elective neck dissection (END) in cases of cT1/2N0 oral cancer presenting with SLN metastasis.

Methods: A prospective cohort of patients with cT1/2N0 oral cancer underwent SLN biopsy using a γ-probe alongside methylene blue staining, followed by subsequent END. The primary outcome variable was non-SLN metastasis, with its predictors evaluated through logistic regression analysis.

Expression of nicastrin, NICD1, and Hes1 in NCSTN knockout mice: implications for hidradenitis suppurativa, Alzheimer's, and liver cancer.

Background: Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce.

Methods: CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J).

Toripalimab plus chemotherapy for first line treatment of advanced non-small cell lung cancer (CHOICE-01): final OS and biomarker exploration of a randomized, double-blind, phase 3 trial.

A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.

Benefits, harms, and cost-effectiveness of risk model-based and risk factor-based low-dose computed tomography screening strategies for lung cancer: a systematic review.

Background: It has been proposed that risk model-based strategies could serve as viable alternatives to traditional risk factor-based approaches in lung cancer screening; however, there has been no systematic discussion. In this review, we provide an overview of the benefits, harms, and cost-effectiveness of these two strategies in lung cancer screening application, as well as discussing possible future research directions.

Methods: Following the PRISMA guidelines, a comprehensive literature search was conducted across PubMed, Web of Science, Cochrane libraries, and EMBASE from January 1994 to April 2024.

ALKBH5 promotes cardiac fibroblasts pyroptosis after myocardial infarction through Notch1/NLRP3 pathway.

Through bioinformatics screening, we previously found that AlkB homolog 5 (ALKBH5) expression, an mA demethylase, was higher in patients with heart failure than in the normal population. This study aimed to investigate the molecular mechanisms by which ALKBH5 regulates heart failure. We established a myocardial infarction (MI)-induced heart failure model in rats in vivo and an in vitro hypoxia model using rat primary cardiac fibroblasts (RCFs).

Effect of an Endoscopy Screening on Upper Gastrointestinal Cancer Mortality: A Community-based Multicenter Cluster Randomized Clinical Trial.

Background And Aims: Population-based observational studies suggest that endoscopic screening may reduce upper gastrointestinal cancer mortality. We aimed to quantify the effect of endoscopy screening.

Methods: This is a community-based, multicenter, cluster randomized clinical trial conducted in both high-risk and non-high-risk areas of China.