Exosomal miR-224-3p promotes lymphangiogenesis and lymph node metastasis by targeting GSK3B in gastric cancer.

Background: Patients with gastric cancer (GC) are prone to lymph node metastasis (LNM), which is an important factor for recurrence and poor prognosis of GC. Nowadays, more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis. An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.

Chain-mediated effect of physical activity between Chinese language-based L2 motivational self-system and intended effort.

The L2 Motivational Self System (L2MSS) determines an individual's motivation in second language learning and influences the learning experience and intended effort. Although physical activity (PA) has been shown to enhance academic efficacy, the role of PA in whether it promotes second language learning efficacy has not been elucidated. Therefore, the present study examined PA as a mediator and explored its ameliorative effects in L2MSS.

First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

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).

Efficacy and safety of multi-target tyrosine kinase inhibitor AL2846 combined with gemcitabine in pancreatic cancer.

Pancreatic cancer patients urgently need new treatments, and we explored the efficacy and safety of combination therapy with AL2846 and gemcitabine in pancreatic cancer patients. This was a single-arm, single-center, open-label phase I/IIa study (NCT06278493). The dose-escalation phase was designed to evaluate the maximum tolerated dose (MTD) of AL2846 combined with gemcitabine.

Effect of Energy Density on Mechanical Properties of NiTiCu Shape Memory Alloys Prepared by SLM.

In the Ni-Ti shape memory alloy system, Cu elements are used to replace Ni elements. A NiTiCu alloy with a molar ratio of 45:50:5 was prepared using laser selective melting technology. The density, composition, microstructure, and mechanical properties of the NiTiCu alloy were investigated.

Multiomics reveals tumor microenvironment remodeling in locally advanced gastric and gastroesophageal junction cancer following neoadjuvant immunotherapy and chemotherapy.

Background: Perioperative chemotherapy is the standard of care for patients with locally advanced gastric and gastroesophageal junction cancer. Recent evidence demonstrated the addition of programmed cell death protein 1 (PD-1) inhibitors enhanced therapeutic efficacy. However, the mechanisms of response and resistance remain largely undefined.

Interpretable multi-modal artificial intelligence model for predicting gastric cancer response to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy assessment is imperative for prognostication and clinical management of locally advanced gastric cancer. We propose an incremental supervised contrastive learning model (iSCLM), an interpretable artificial intelligence framework integrating pretreatment CT scans and H&E-stained biopsy images, for improved decision-making regarding neoadjuvant chemotherapy. We have constructed and tested iSCLM using retrospective data from 2,387 patients across 10 medical centers and evaluated its discriminative ability in a prospective cohort (132 patients; ChiCTR2300068917).

Efficacy and Safety of KH903 Plus FOLFIRI as a Second-Line Treatment in Unresectable Recurrent or Metastatic Colorectal Cancer: A Randomized Phase 2 Study.

Background: Patients with recurrent or metastatic advanced colorectal cancer (mCRC) often face the clinical dilemma as this unresectable disease is continuously progressing and endangering the patients' lives. In the current study, we explored the clinical feasibility of KH903 in combination with FOLFIRI chemotherapy as a new clinical indication for mCRC.

Methods: Patients (N = 122) were randomized 1:1 to 4mg/kg q1w KH903 or 5mg/kg q2w KH903, and both groups of patients were treated with the fixed regimen of FOLFIRI (every 2 weeks) along with the KH903 therapy.

Inhibitory effects of circR-127aa on gastric cancer progression and tumor growth.

This study investigates the function of a newly identified 127-amino acid peptide, circR-127aa, encoded by hsa_circ_0075402 (circRACK1), in gastric cancer (GC), a condition with significant prevalence in China. Utilizing a comprehensive analysis of circular RNA (circRNA) ribosome profiling data alongside experimental validations through mass spectrometry, Western blot, and immunofluorescence, we demonstrate that circR-127aa Inhibits Malignant Phenotypes and suppresses tumor growth in nude mice models. Significantly, the interaction of circR-127aa with Vimentin, a crucial element in actin-actin-cytoskeletal remodeling, indicates that circR-127aa functions as a tumor suppressor by facilitating the ubiquitination of Vimentin.

Clinicopathological Characteristics and Perioperative Treatment of Epstein-Barr Virus-Associated Gastric Cancer: A Retrospective Study.

Introduction: The clinicopathological characteristics and efficacy of perioperative treatment of Epstein-Barr virus-associated gastric cancer (EBVaGC) were investigated.

Methods: The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed, and Cox regression analysis was performed to identify risk factors.

Feasibility and Safety of PD-1 Blockades Among Elderly Patients with Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Study.

Objective: This study aimed to identify the effectiveness and safety of PD-1 blockades among elderly patients with metastatic esophageal squamous cell carcinoma (ESCC) clinically.

Methods: A total of 78 elderly patients with previously treated metastatic ESCC aged ≥65 years who received PD-1 blockades monotherapy were included retrospectively. Demographic characteristics, therapeutic effectiveness and adverse reactions of the elderly patients who underwent PD-1 blockade therapy were recorded.

A spatiotemporal comparative analysis on tumor immune microenvironment characteristics between neoadjuvant chemotherapy and preoperative immunotherapy for ESCC.

The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

Background: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS.

Methods: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m) and cisplatin (75 mg/m).

Erratum: Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis: Erratum.

[This corrects the article DOI: 10.7150/thno.44419.

Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study.

Background: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC.

Methods: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened.

Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

Background: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity.

Methods: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause.

Tyrosine phosphatase SHP2 aggravates tumor progression and glycolysis by dephosphorylating PKM2 in gastric cancer.

Gastric cancer (GC) is among the most lethal human malignancies, yet it remains hampered by challenges in fronter of molecular-guided targeted therapy to direct clinical treatment strategies. The protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) is involved in the malignant progression of GC. However, the detailed mechanisms of the posttranslational modifications of SHP2 remain poorly understood.

Effect of different exercise modalities on nonalcoholic fatty liver disease: a systematic review and network meta-analysis.

Physical exercise intervention can significantly improve the liver of patients with Non-alcoholic fatty liver disease (NAFLD), but it is unknown which exercise mode has the best effect on liver improvement in NAFLD patients. Therefore, we systematically evaluated the effect of exercise therapy on liver and blood index function of NAFLD patients through network meta-analysis (NMA). Through systematic retrieval of PubMed, Cochrane Library, Web of Science, EBSCO, and CNKI (National Knowledge Infrastructure), two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies by means of databases from inception to January 2023.

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

Background: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy.

Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells.

Different from necrosis, apoptosis, autophagy and other forms of cell death, ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated fatty acids under the action of iron divalent or lipoxygenase, leading to cell death. Apatinib is currently used in the third-line standard treatment of advanced gastric cancer, targeting the anti-angiogenesis pathway. However, Apatinib-mediated ferroptosis in vascular endothelial cells has not been reported yet.