Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.

Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.

A Brief Review of Recent Theoretical Advances in Fe-Based Catalysts for CO2 Hydrogenation.

Catalytic hydrogenation presents a promising approach for converting CO2 into valuable chemicals and fuels, crucial for climate change mitigation. Iron-based catalysts have emerged as key contributors, particularly in driving the reverse water-gas shift and Fischer-Tropsch synthesis reactions. Recent research has focused on enhancing the efficiency and selectivity of these catalysts by incorporating alkali metal promoters or transition metal dopants, enabling precise adjustments to their composition and properties. This review synthesizes recent theoretical advancements in CO2 hydrogenation with iron-based catalysts, employing density functional theory and microkinetic modeling. By elucidating the underlying mechanisms involving metallic iron, iron oxides, and iron carbides, we address current challenges and provide insights for future sustainable CO2 hydrogenation developments.

Research Progress of Non-Noble Metal Catalysts for Carbon Dioxide Methanation.

The extensive utilization of fossil fuels has led to a rapid increase in atmospheric CO2 concentration, resulting in various environmental issues. To reduce reliance on fossil fuels and mitigate CO2 emissions, it is important to explore alternative methods of utilizing CO2 and H2 as raw materials to obtain high-value-added chemicals or fuels. One such method is CO2 methanation, which converts CO2 and H2 into methane (CH4), a valuable fuel and raw material for other chemicals. However, CO2 methanation faces challenges in terms of kinetics and thermodynamics. The reaction rate, CO2 conversion, and CH4 yield need to be improved to make the process more efficient. To overcome these challenges, the development of suitable catalysts is essential. Non-noble metal catalysts have gained significant attention due to their high catalytic activity and relatively low cost. In this paper, the thermodynamics and kinetics of the CO2 methanation reaction are discussed. The focus is primarily on reviewing Ni-based, Co-based, and other commonly used catalysts such as Fe-based. The effects of catalyst supports, preparation methods, and promoters on the catalytic performance of the methanation reaction are highlighted. Additionally, the paper summarizes the impact of reaction conditions such as temperature, pressure, space velocity, and H2/CO2 ratio on the catalyst performance. The mechanism of CO2 methanation is also summarized to provide a comprehensive understanding of the process. The objective of this paper is to deepen the understanding of non-noble metal catalysts in CO2 methanation reactions and provide insights for improving catalyst performance. By addressing the limitations of CO2 methanation and exploring the factors influencing catalyst effectiveness, researchers can develop more efficient and cost-effective catalysts for this reaction.

The biological role of extracellular vesicles in gastric cancer metastasis.

Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition (EMT) and mesothelial-mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer.

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/ß-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival.

Hospital volume-mortality association after esophagectomy for cancer: a systematic review and meta-analysis.

BACKGROUND: Postoperative mortality plays an important role in evaluating the surgical safety of esophagectomy. Although postoperative mortality after esophagectomy is partly influenced by the yearly hospital surgical case volume (hospital volume), this association remains unclear. METHODS: Studies assessing the association between hospital volume and postoperative mortality in patients who underwent esophagectomy for esophageal cancer were searched for eligibility. Odds ratios were pooled for the highest versus lowest categories of hospital volume using a random effects model. The dose-response association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with PROSPERO. RESULTS: Fifty-six studies including 385 469 participants were included. A higher-volume hospital significantly reduced the risk of postesophagectomy mortality by 53% compared with their lower-volume counterparts (odds ratio, 0.47; 95% CI: 0.42-0.53). Similar results were found in subgroup analyses. Volume-outcome analysis suggested that postesophagectomy mortality rates remained roughly stable after the hospital volume reached a plateau of 45 esophagectomies per year. CONCLUSIONS: Higher-volume hospitals had significantly lower postesophagectomy mortality rates in patients with esophageal cancer, with a threshold of 45 esophagectomies per year for a high-volume hospital. This remarkable negative correlation showed the benefit of a better safety in centralization of esophagectomy to a high-volume hospital.

Methylation synthetic lethality: Exploiting selective drug targets for cancer therapy.

In cancer, synthetic lethality refers to the drug-induced inactivation of one gene and the inhibition of another in cancer cells by a drug, resulting in the death of only cancer cells; however, this effect is not present in normal cells, leading to targeted killing of cancer cells. Recent intensive epigenetic research has revealed that aberrant epigenetic changes are more frequently observed than gene mutations in certain cancers. Recently, numerous studies have reported various methylation synthetic lethal combinations involving DNA damage repair genes, metabolic pathway genes, and paralogs with significant results in cellular models, some of which have already entered clinical trials with promising results. This review systematically introduces the advantages of methylation synthetic lethality and describes the lethal mechanisms of methylation synthetic lethal combinations that have recently demonstrated success in cellular models. Furthermore, we discuss the future opportunities and challenges of methylation synthetic lethality in targeted anticancer therapies.

Reuterin promotes pyroptosis in hepatocellular cancer cells through mtDNA-mediated STING activation and caspase 8 expression.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor prognosis. The available drugs for advanced HCC are limited and substantial therapeutic advances including new drugs and new combination therapies are still in urgent need. In this study, we found that the major metabolite of Lactobacillus reuteri (L. reuteri), reuterin showed great anti-HCC potential and could help in sorafenib treatment. Reuterin treatment impaired mitophagy and caused the aberrant clustering of mitochondrial nucleoids to block mitochondrial DNA (mtDNA) replication and mitochondrial fission, which could promote mtDNA leakage and subsequent STING activation in HCC cells. STING could activate pyroptosis and necroptosis, while reuterin treatment also induced caspase 8 expression to inhibit necroptosis through cleaving RIPK3 in HCC cells. Thus, pyroptosis was the main death form in reuterin-treated HCC cells and STING suppression remarkably rescued the growth inhibitory effect of reuterin and concurrently knockdown caspase 8 synergized to restrain the induction of pyroptosis. In conclusion, our study explains the detailed molecular mechanisms of the antitumor effect of reuterin and reveals its potential to perform as a combinational drug for HCC treatment.