Treatment Of Gastric Cancer Research Articles

Colorectal endoscopic submucosal dissection in the USA: The current state and future perspectives.

Endoscopic submucosal dissection (ESD) is a transformative advancement in the endoscopic management of superficial gastrointestinal lesions. Initially conceived for the treatment of early gastric cancer, ESD has demonstrated proficiency in achieving en-bloc resection of superficial gastrointestinal lesions. ESD has experienced widespread acceptance in Japan and East Asia; however, its adoption in the USA remains delayed. This initial hesitancy could be attributed to procedural complexity and training demands; nonetheless, recently, ESD has been gaining popularity in the USA. This is due to the advancements in endoscopic technology, tailored training programs, and cumulative evidence regarding the efficacy and safety of ESDs. This review aimed to deliberate the historical progress, current implementation, and prospective trajectory of ESDs in the USA. With ongoing clinical research, technological integration, and educational efforts, ESD is likely to become the gold standard for managing large gastrointesitinal lesions. This progress marks an imperative step toward less invasive, more precise, and patient-centric approaches regarding advanced therapeutic endoscopy in the USA.

Gastrectomies for the treatment of gastric cancer in a reference cancer center present better pathological results and survival compared to non‐specialized hospitals

Gastrectomies for the treatment of gastric cancer in a reference cancer center present better pathological results and survival compared to non‐specialized hospitals

Diagnosis to dissection: AI's role in early detection and surgical intervention for gastric cancer.

Gastric cancer remains a formidable health challenge worldwide; early detection and effective surgical intervention are critical for improving patient outcomes. This comprehensive review explores the evolving landscape of gastric cancer management, emphasizing the significant contributions of artificial intelligence (AI) in revolutionizing both diagnostic and therapeutic approaches. Despite advancements in the medical field, the subtle nature of early gastric cancer symptoms often leads to late-stage diagnoses, where survival rates are notably decreased. Historically, the treatment of gastric cancer has transitioned from palliative care to surgical resection, evolving further with the introduction of minimally invasive surgical (MIS) techniques. In the current era, AI has emerged as a transformative force, enhancing the precision of early gastric cancer detection through sophisticated image analysis, and supporting surgical decision-making with predictive modeling and real-time preop-, intraop-, and postoperative guidance. However, the deployment of AI in healthcare raises significant ethical, legal, and practical challenges, including the necessity for ongoing professional education and the development of standardized protocols to ensure patient safety and the effective use of AI technologies. Future directions point toward a synergistic integration of AI with clinical best practices, promising a new era of personalized, efficient, and safer gastric cancer management.

SMARCD3 Overexpression Promotes Epithelial-Mesenchymal Transition in Gastric Cancer.

This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan-Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16, p < 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial-mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p < 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p < 0.05), and in KATO III cells, it increased β-catenin and PI3Kp85 activities (p < 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT.

Clinical complete response after trastuzumab deruxtecan 6th-line treatment for postoperative gastric cancer recurrence: a case report

BackgroundDespite the recent developments in the treatment of advanced or recurrent gastric cancer, the median survival time remains shorter than 15 months. Herein, we report a case of postoperative gastric cancer recurrence in which a complete clinical response was achieved with trastuzumab deruxtecan as 6th-line treatment.Case presentationA 70-year-old man underwent abdominal contrast-enhanced computed tomography (CT) during follow-up after rectal cancer surgery. The CT revealed an enlarged perigastric lymph node. After further examination, the patient’s condition was diagnosed as gastric cancer cT2N1H0P0M0 cStage IIA. The patient underwent distal gastrectomy and D2 lymph node dissection. The resulting pathological diagnosis was pT1bN3aH0P0 pStageIIB, HER2 score 3+. Abdominal contrast-enhanced CT 19 months postoperatively revealed para-aortic lymph node recurrence, thus systemic chemotherapy courses were planned. The primary treatment was a combination of S-1, cisplatin, and trastuzumab administered in 11 courses. However, there was an enlargement of the para-aortic lymph node which was evaluated as progressive disease. Systematic chemotherapy with various regimens was continued until the 5th-line treatment. However, therapeutic benefits were not achieved and lung metastasis was observed. Trastuzumab deruxtecan (TDXD) was initiated as 6th-line treatment. Abdominal contrast-enhanced CT at 4 months after the start of treatment showed marked shrinkage of the enlarged para-aortic lymph node and disappearance of the lung metastasis in the right upper lung lobe, which was evaluated as partial response (PR). The para-aortic lymph node metastasis was evaluated as PR with only a slight accumulation of SUV-Max 2.66 with a shrinking trend by positron emission tomography-computed tomography (PET-CT) performed after 1 year. Tumor markers CEA, CA19-9, and CA125 also improved significantly. PET-CT after 1 year and 4 months showed no lymph node enlargement or accumulation, indicating a complete response (CR). All tumor markers also normalized. The patient has maintained clinical CR without additional treatment to date.ConclusionsWe report the apparent first case of postoperative gastric cancer recurrence successfully treated with TDXD, achieving clinical CR with TDXD as a 6th-line treatment.

Advanced Gastric Cancer: CT Radiomics Prediction of Lymph Modes Metastasis After Neoadjuvant Chemotherapy.

This study aims to create and assess machine learning models for predicting lymph node metastases following neoadjuvant treatment in advanced gastric cancer (AGC) using baseline and restaging computed tomography (CT). We evaluated CT images and pathological data from 158 patients with resected stomach cancer from two institutions in this retrospective analysis. Patients were eligible for inclusion if they had histologically proven gastric cancer. They had received neoadjuvant chemotherapy, with at least 15 lymph nodes removed. All patients received baseline and preoperative abdominal CT and had complete clinicopathological reports. They were divided into two cohorts: (a) the primary cohort (n = 125) for model creation and (b) the testing cohort (n = 33) for evaluating models' capacity to predict the existence of lymph node metastases. The diagnostic ability of the radiomics-model for lymph node metastasis was compared to traditional CT morphological diagnosis by radiologist. The radiomics model based on the baseline and preoperative CT images produced encouraging results in the training group (AUC 0.846) and testing cohort (AUC 0.843). In the training cohort, the sensitivity and specificity were 81.3% and 77.8%, respectively, whereas in the testing cohort, they were 84% and 75%. The diagnostic sensitivity and specificity of the radiologist were 70% and 42.2% (using baseline CT) and 46.3% and 62.2% (using preoperative CT). In particular, the specificity of radiomics model was higher than that of conventional CT in diagnosing N0 cases (no lymph node metastasis). The CT-based radiomics model could assess lymph node metastasis more accurately than traditional CT imaging in AGC patients following neoadjuvant chemotherapy.

Identification and validation of the role of ZNF281 in 5-fluorouracil chemotherapy of gastric cancer

BackgroundThe early diagnosis of gastric cancer (GC) and overcoming chemotherapy resistance is challenging. The aberrant expression of zinc finger protein 281 (ZNF281) and the over-activation of the Wnt/β-catenin pathway are oncogenic factors and confer tumor chemoresistance. ZNF281 modulates the Wnt/β-catenin pathway to influence malignant tumor behavior. However, the role of ZNF281 in GC chemotherapy and the relationship with the Wnt/β-catenin pathway have not been elucidated by researchers.MethodsWe explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281’s role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/β-catenin pathway proteins.ResultsZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/β-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells.ConclusionWe identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/β-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.

Laparoscopic versus open total gastrectomy for T4a gastric cancer: a propensity score-matched analysis of long-term outcomes.

Evidence of implementation of laparoscopic total gastrectomy (LTG) for surgical T4a stage (sT4a) gastric cancer (GC) remains inadequate. This study aimed to compare short- and long-term outcomes of LTG versus open total gastrectomy(OTG) for sT4a GC. This retrospective cohort study was conducted using data from patients with sT4a GC underwent total gastrectomy from 2014 to 2020. Short-term outcomes included operative characteristics and postoperative complications. Long-term oncological outcomes focused on 3-, and 5-year overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) was applied to reduce potential biases in baseline characteristics between groups. There was a total of 161 patients, in which 96 underwent LTG and 65 underwent OTG. After PSM, both groups consisted of 51 patients each, with balanced baseline characteristics. There were no significant differences between the two groups regarding blood loss, length of proximal resected margin, postoperative hospital stays, and overall and major postoperative complications. Most of the complications were classified as minor according to the Clavien-Dindo classification. Operating time was significantly longer in the LTG group (mean: 257min vs. 231min, p = 0.006). LTG was superior to OTG groups in time to flatus (mean: 3.0 days vs 3.9 days, p < 0.001). Five-year OS and DFS rates were similar between the two groups (44% and 33% vs. 43% and 28% in the LTG and OTG groups, respectively). Our findings indicate that LTG is a feasible and safe technique, exhibiting comparable long-term oncological outcomes to OTG for sT4a GC. LTG may be an acceptable alternative to OTG for the treatment of sT4a GC.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer.

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Engineered low-pathogenic Helicobacter pylori as orally tumor immunomodulators for the stimulation of systemic immune response

Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.

Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update.

Many studies on gastric cancer treatment have identified predictors of immunotherapy benefits. This article provides an update on the major developments in research related to predictive factors of immunotherapy for gastric cancer. We used the search term "predictive factors, immunotherapy, gastric cancer" to find the most current publications in the PubMed database related to predictive factors of immunotherapy in gastric cancer. Programmed cell death, genetic, and immunological factors are the main study topics of immunotherapy's predictive factors in gastric cancer. Other preventive factors for immunotherapy in gastric cancer were also found, including clinical factors, tumor microenvironment factors, imaging factors, and extracellular factors. Since there is currently no effective treatment for gastric cancer, we strongly propose that these studies be prioritized.

Epstein-Barr virus deubiquitinating enzyme BPLF1 is involved in EBV carcinogenesis by affecting cellular genomic stability

Increased mutational burden and EBV load have been revealed from normal tissues to Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs). BPLF1, encoded by EBV, is a lytic cycle protein with deubiquitinating activity has been found to participate in disrupting repair of DNA damage. We first confirmed that BPLF1 gene in gastric cancer (GC) significantly increased the DNA double strand breaks (DSBs). Ubiquitination mass spectrometry identified histones as BPLF1 interactors and potential substrates, and co-immunoprecipitation and in vitro experiments verified that BPLF1 regulates H2Bub by targeting Rad6. Over-expressing Rad6 restored H2Bub but partially reduced γ-H2AX, suggesting that other downstream DNA repair processes were affected. mRNA expression of BRCA2 were significantly down-regulated by next-generation sequencing after over-expression of BPLF1, and over-expression of p65 facilitated the repair of DSBs. We demonstrated BPLF1 may lead to the accumulation of DSBs by two pathways, reducing H2B ubiquitination (H2Bub) and blocking homologous recombination which may provide new ideas for the treatment of gastric cancer.

Molecular mechanism of Saikosaponin-d in the treatment of gastric cancer based on network pharmacology and in vitro experimental verification.

The study aimed to utilize network pharmacology combined withcell experiments to research the mechanism of action of Saikosaponin-d in the treatment of gastric cancer. Drug target genes were obtained from the PubChem database and the Swiss Target Prediction database. Additionally, target genes for gastric cancer were obtained from the GEO database and the Gene Cards database. The core targets were then identified and further analyzed through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GESA enrichment. The clinical relevance of the core targets was assessed using the GEPIA and HPA databases. Molecular docking of drug monomers and core target proteins was performed using Auto Duck Tools and Pymol software. Finally, in vitro cellular experiments including cell viability, apoptosis, cell scratch, transwell invasion, transwell migration, qRT-PCR, and Western blot were conducted to verify these findings of network pharmacology. The network pharmacology analysis predicted that the drug monomers interacted with 54 disease targets. Based on clinical relevance analysis, six core targets were selected: VEGFA, IL2, CASP3, BCL2L1, MMP2, and MMP1. Molecular docking results showed binding activity between the Saikosaponin-d monomer and these core targets. Saikosaponin-d could inhibit gastric cancer cell proliferation, induce apoptosis, and inhibit cell migration and invasion.

How to measure quality of surgery as a component of multimodality treatment of gastric cancer.

Gastric cancer (GC) is one of the most frequent reasons for cancer-related death worldwide. The multimodal therapeutic strategies are now pragmatically tailored to each patient, especially in advanced GC. A radical but safe gastrectomy remains the cornerstone of the GC treatment. Moreover, the quality-of-life (QoL) outcome measures are now routinely utilized in order to select optimal type of gastrectomy, as well as reconstruction method. Postoperative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. The postoperative complications prolong hospital stay and may result in poor QoL, thus eliminating the completion of perioperative adjuvant therapy. Therefore, avoiding morbidity is not only relevant for the immediate postoperative course, but can also affect long-term oncological outcome. Measuring outcome enables surgeons to: monitor their own results; compare quality of treatment between centres; facilitate improvement both for surgery alone and combined treatment; select optimal procedure for an individual patient. Textbook oncological outcome is a composite quality measure representing the ideal hospitalization for gastrectomy, as well as stage-appropriate (perioperative) adjuvant chemotherapy. Standardized system for recording complications and adherence to multimodality treatment guidelines are crucial for achieving the ultimate goal of surgical quality-improvement that can benefit patients QoL and long-term outcomes after fast and uneventful hospitalization for gastrectomy.

Immunotherapy Based on Immune Checkpoint Molecules and Immune Checkpoint Inhibitors in Gastric Cancer-Narrative Review.

Due to its rapid progression to advanced stages and highly metastatic properties, gastric cancer (GC) is one of the most aggressive malignancies and the fourth leading cause of cancer-related deaths worldwide. The metastatic process includes local invasion, metastasis initiation, migration with colonisation at distant sites, and evasion of the immune response. Tumour growth involves the activation of inhibitory signals associated with the immune response, also known as immune checkpoints, including PD-1/PD-L1 (programmed death 1/programmed death ligand 1), CTLA-4 (cytotoxic T cell antigen 4), TIGIT (T cell immunoreceptor with Ig and ITIM domains), and others. Immune checkpoint molecules (ICPMs) are proteins that modulate the innate and adaptive immune responses. While their expression is prominent on immune cells, mainly antigen-presenting cells (APC) and other types of cells, they are also expressed on tumour cells. The engagement of the receptor by the ligand is crucial for inhibiting or stimulating the immune cell, which is an extremely important aspect of cancer immunotherapy. This narrative review explores immunotherapy, focusing on ICPMs and immune checkpoint inhibitors in GC. We also summarise the current clinical trials that are evaluating ICPMs as a target for GC treatment.

Metformin suppresses gastric cancer progression by disrupting the STAT1-PRMT1 axis

Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.

Silver nanoparticles stabilized by chitosan-polyvinyl alcohol polymers mediated by Pistacia extract for treatment of functional dyspepsia and gastric cancer

The impact of the nanoparticles on the dyspepsia mice gut microbiota is evaluated through the utilization of the 16S rRNA technique. Various methods were employed to characterize the NPs. In the textile, culinary, paper, leather, and printing sectors, synthetic dyes are frequently employed as coloring agents. Because these dye molecules are harmful to both the environment and living things, it is difficult to remove them sustainably. Here, we have produced nanoparticles embedded in chitosan-polyvinyl alcohol hydrogel (CS-PVA) by using bark's Pistacia under ultrasonic irradiation. The reduction of Ag + ions into Ag0 NPs was detected by a visual change in the colors. UV–Vis analysis indicated that the characteristic SPR band appeared near ∼440–450 nm. UV/Vis, EDX-elemental mapping, SEM, TEM, ICP-OES, and XRD analysis were applied to characterize the Ag NPs/CS-PVA nanocomposite. The recent study focused on the cellular and molecular aspects. The MTT assay was conducted for 48 h to evaluate the anti-human gastric cancer and cytotoxicity efficacies of the treated cells with nanocomposite. The assessment was performed on normal (HUVEC) and gastric cancer cells, namely MKN45 and NCI–N87. The IC50 values of nanocomposite against MKN45 and NCI–N87 were 180 and 151 μg/mL, respectively. The dose-dependent reduction in malignant gastric cell viability was observed in the nanocomposite presence. Furthermore, the nanocomposite induced cell apoptosis by 40–50%, leading to an increase in the expression of pro-apoptotic markers (Bax and cleaved caspase-8) and a decrease in the expression of the anti-apoptotic marker, Bcl-2. Furthermore, the nanocomposite showed inhibitory effects on colony formation. Our results indicate that the nanocomposite can increase p53 expression and decrease the expression of STAT3 in treated cells. This indicates that p53 and STAT3 play crucial roles in the biological effects induced by the extract in human gastric carcinoma cells. The data from the gut microbiome suggested that nanocomposites have the ability to control the rebalancing of homeostasis and microbiome composition by decreasing the levels of harmful bacteria, and at the same time, increasing the levels of beneficial bacteria. Following the introduction of nanocomposite, there was an observed rise in the levels of gastrointestinal hormones in the serum, including gastrin and motilin, while the levels of vasoactive intestinal peptide decreased. The application of nanocomposite led to an improvement in gastrointestinal movement, encompassing a rise in the rate of transit through the small intestine and the rate of gastric emptying. These findings offer that the Ag NPs/CS-PVA nanocomposite could be a promising anticancer treatment for functional dyspepsia and gastric cancer.

The effect of LNCRNA SHANK3 on the malignant development of gastric cancer cells by regulating the miR-4530/MNX1

Gastric cancer (GC) has become the first malignant tumor with highest incidence rate and mortality of cancer in China, finding therapeutic targets for gastric cancer is of great significant for improving the survival rate of patients with GC. Recently, many of studies have shown that LncRNAs is involved in multiple biological progresses in the development of GC. This study, we screened for abnormally high expression of LncSHANK3 in GC through the TCGA database, and found that LncSHANK3 sponge adsorbs miR-4530, further competing with MNX1 and binding to miR-4530. We demonstrated the interaction between LncSHANK3 and miR-4530 through luciferase reporting analysis, with miR-4530 negatively regulating MNX1.Through CCK8, colony formation, transwell, and wound healing assays, it was found that LncSHANK3 affects the occurrence of GC through cell proliferation, migration and invasion. In conclusion, LncSHANK3/miR-4530/MNX1 axis is a potential mechanism for the treatment of GC.

Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer

In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology . We focus specifically on the application of immune checkpoint inhibitors (ICIs) and microsatellite instability (MSI) in gastric cancer (GC). The four pillars of GC management have long been considered, including surgery, chemotherapy, radiotherapy and targeted therapy. However, immunotherapy has recently emerged as a ”fifth pillar”, and its use is rapidly expanding. There are four principal strategies for tumor immunotherapy: ICIs, tumor vaccines, adoptive immunotherapy and nonspecific immunomodulators. Of them, ICIs are the most advanced and widespread type of cancer immunotherapy for GC. Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy. In particular, inhibition of the PD-1/PD-L1 axis with ICIs, including nivolumab and pembrolizumab, has emerged as a novel treatment strategy for advanced GC. Unfortunately, these therapies are sometimes associated with often subtle, potentially fatal immune-related adverse events (irAEs), including dermatitis, diarrhea, colitis, endocrinopathy, hepatotoxicity, neuropathy and pneumonitis. We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges, emergency department revisits, and downstream complications. Recent studies have revealed that MSI-high or mismatch- repair-deficient tumors, regardless of their primary site, have a promising response to ICIs. So, it is important to detect MSI before applying ICIs for treatment of GC.

In vitro assessment of the genotoxic and cytotoxic effects of clarified açai (Euterpe oleracea MART) extract in a gastric cancer cell line (AGP01 cells).

Açaí (Euterpe oleracea MART) is a fruit of great importance for the Amazon region in nutritional, cultural and socioeconomic terms. In recent years, açaí has been the subject of several studies due to its beneficial properties for health, including effects against tumor cells. Therefore, the present work aimed to evaluate in vitro the genotoxic and cytotoxic effects of the clarified extract of açaí juice in a human metastatic gastric cancer cell line (AGP01 cells). For comparison purposes, a non-transformed cell line of African green monkey renal epithelial cells (VERO cells) was used. The viability assay by resazurin reduction, the comet assay, the determination of cell death by differential fluorescent dyes and the wound healing migration assay were performed. A reduction in viability was observed only in the AGP01 line within 72 h. There was no genotoxic damage or cell death (through apoptosis or necrosis) in any of the cell lines. However, açaí extract induced motility reduction in both cell lines. The reduction in cell viability and the induction of the anti-migratory effect in the AGP01 cell line opens perspectives for exploring the potential of açaí as an adjuvant in the treatment of gastric cancer.