Treatment Of Gastric Cancer Research Articles

LINC01224 promotes the Warburg effect in gastric cancer by activating the miR-486-5p/PI3K axis.

The Warburg effect, a common feature of solid tumors, rewires the metabolism and promotes growth, survival, proliferation, and long-term maintenance in gastric cancer (GC). We performed in vitro and in vivo studies of the pathogenesis of GC to investigate the effects and mechanism of LINC01224 in this cancer. qRT-PCR was used to measure the expression of LINC01224 or miR-486-5p in GC cells, and the expression of LINC01224 in GC tissues by FISH (Fluorescence in situ hybridization) analysis was evaluated. Bioinformatics predicted the target gene of LINC01224, Western blotting was used to measure the protein expression of genes in the PI3K/AKT/mTOR/HIF-1α axis and Warburg effect in GC cells. The function of LINC01224 in GC cells was determined using measurements of EDU assay, colony formation, apoptosis, cell migration, and cell invasion. Glucose metabolism was evaluated using a glucose uptake assay and measurements of lactate. A tumor xenograft model was used to examine the effect of LINC01224 on GC growth in vivo. We found that upregulation of LINC01224 in GC cells activated the miR-486-5p/PI3K axis and promoted aerobic glycolysis, thereby increasing cell viability, proliferation, migration, invasion and anti-apoptosis. LINC01224 downregulation had the opposite effect. LINC01224 expression promoted the in vitro and in vivo pathogenesis of GC by promoting aerobic glycolysis. LINC01224 is a promising target in the treatment of GC.

Construction and validation of a nomogram prediction model for the occurrence of complications in patients following robotic radical surgery for gastric cancer.

In the last two decades, robotic-assisted gastrectomy has become a widely adopted surgical option for gastric cancer (GC) treatment. Despite its popularity, postoperative complications can significantly deteriorate patient quality of life and prognosis. Therefore, identifying risk factors for these complications is crucial for early detection and intervention. This research is designed to construct and validate a predictive model for assessing the risk of postoperative complications in patients undergoing robotic-assisted radical gastrectomy. A retrospective analysis was conducted on 500 GC patients from Gansu Provincial People's Hospital between December 2016 and October 2023. These patients formed the training cohort. An additional 136 patients from the 940th Hospital of Joint Logistic Support Force, the Chinese People's Liberation Army as the external validation cohort. Patients were categorized into groups with and without complications. Data collected included demographic details, laboratory results, CT quantitative body composition analysis, and clinical information. Variable selection was conducted through Lasso regression, succeeded by multivariable logistic regression to pinpoint independent risk factors. These elements facilitated the construction of a nomogram for prediction. The model's performance underwent internal validation via bootstrap techniques and external validation through a validation cohort. The efficacy of the model was quantified by the area under the receiver operating characteristic (ROC) curve (AUC), evaluated for calibration using calibration curves and the Hosmer-Lemeshow test, and assessed for clinical utility through decision curve analysis (DCA). Of the 500 patients in the training cohort, 65 experienced complications, a rate of 13%. The validation cohort had a similar complication rate of 13.24% (18 out of 136 patients). Independent risk factors identified included tumor diameter (OR = 1.99, 95% CI = 1.07-3.73), TNM stage III (OR = 2.12, 95% CI = 1.03-4.36), ASA class I (OR = 0.26, 95% CI = 0.13-0.53), ASA class III (OR = 4.75, 95% CI = 2.12-10.62), and visceral fat area (VFA) (OR = 2.52, 95% CI = 1.10-5.79). The nomogram demonstrated good discrimination (AUC = 0.81, 95% CI: 0.76-0.87) in internal validation and (AUC = 0.79, 95% CI: 0.67-0.90) in external validation. Both validations confirmed the model's accurate calibration and significant clinical utility, with net benefits observed at probability thresholds ranging from 2 to 79% and 2-71%. The developed nomogram, based on five independent risk factors-tumor diameter, TNM stage III, ASA class I, ASA class III, and VFA-effectively predicts the risk of complications in patients undergoing robotic-assisted radical gastrectomy, offering a valuable tool for clinical decision-making.

Characterization of Bozitinib as a potential therapeutic agent for MET-amplified gastric cancer

Hyperactive c-Met signaling pathway caused by altered MET is a common mechanism underlying gastric cancer and represents an attractive target for the treatment of gastric cancer with MET alterations. However, no c-Met kinase inhibitors are currently approved specifically for the treatment of c-Met-amplified gastric cancer. Recently, bozitinib, a highly selective c-Met kinase inhibitor, has shown remarkable potency in selectively inhibiting MET-altered non-small cell lung cancer and secondary glioblastoma. In this study, we investigate the antitumor activity of bozitinib against MET-amplified gastric cancer and elucidate its molecular mechanism. Bozitinib demonstrates a strong effect on MET-amplified gastric cancer cells by blocking the c-Met signaling pathway, leading to the inhibition of cell proliferation and survival, as well as the induction of G0/G1 phase arrest and apoptosis. Structurally, bozitinib is optimally embedded in the ATP pocket of c-Met and firmly binds via an extensive interaction network. In addition, bozitinib efficiently inhibits c-Met resistance-conferring mutations G1163R and Y1230H, although its potency is significantly decreased against the D1228N and Y1230C mutations. Overall, our study reveals the molecular mechanism of bozitinib against c-Met, highlights its ability to overcome acquired resistance mutations, and provides valuable insights into further design and improvement of selective c-Met inhibitors.

Beta-sitosterol regulates PTGS1 to inhibit gastric cancer cell proliferation and angiogenesis.

Gastric cancer (GC) is the third leading culprit of cancer-related deaths around the world. Beta-sitosterol (BS) is an important phytosterol that has been proven to have anti-proliferative effects on GC and other tumors. However, mechanisms and targets of BS in cancer are rarely explored. In this investigation, the targets of BS in the treatment of GC were analyzed by network pharmacology. Molecular docking and cellular thermal shift assay were introduced to validate the binding relationship between BS and PTGS1. The impacts of BS on GC cell viability, half maximal inhibitory concentration, proliferation ability, apoptosis level, and angiogenesis ability were detected by using Cell Counting Kit-8, clone formation assay, flow cytometry, and angiogenesis experiment, respectively. In addition, the expression levels of angiogenic factors (VEGF, FGF, PAI-1) were detected by using western blot. In this project, through cell experiments, PTGS1 was identified as a protein that directly binds to BS. In vitro cell experiments revealed that BS promoted apoptosis and inhibited GC cell proliferation and angiogenesis. Importantly, treatment with BS attenuated the promoting influence of PTGS1 overexpression on GC cell proliferation and angiogenesis. This investigation highlighted PTGS1 as the target of BS in GC cells. BS can regulate PTGS1 to inhibit GC cell proliferation and angiogenesis, providing new evidence for the potential use of BS as a therapeutic agent for GC.

The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine

The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine

Gold Nanorods Decorated by Conjugated Microporous Polymers for Infrared Responsive Cytostatic Drug Delivery.

Near-infrared (NIR) controlled drug delivery systems have drawn a lot of attention throughout the past few decades due to the deep penetration depth and comparatively minor side effects of the stimulus. In this study, we introduce an innovative approach for gastric cancer treatment by combining photothermal infrared-sensitive gold nanorods (AuNRs) with a conjugated microporous polymer (CMP) to create a drug delivery system tailored for transporting the cytostatic drug 5-fluorouracil (5-FU). CMPs are fully conjugated networks with high internal surface areas that can be precisely tailored to the adsorption and transport of active compounds through the right choice of chemical functionalities. By incorporation of surfactant-stabilized AuNRs into the CMP synthesis in dimethylformamide (DMF) the surfactant shell is destabilized and subsequently replaced by the CMP. Particularly, low initial surfactant concentrations led to uniform distribution of the AuNRs in the polymer matrix. Importantly, the integrated AuNRs maintain their plasmonic properties, as was confirmed via electron energy loss spectroscopy. Therefore, the significant photothermal properties are translated to the hybrid material as shown in a proof-of-principle experiment. Further, in an approximated gastric environment, 5-FU release studies were conducted with and without NIR stimulus. Thereby it was observed that increased Brownian motion due to the NIR irradiation not only accelerates the release but also increases the total released amount by influencing the adsorption-desorption equilibrium. This remarkable level of control of the release process underlines the immense potential of this hybrid material for precise and targeted drug delivery.

A Golgi apparatus‑related subtype and risk signature predicts prognosis and evaluates immunotherapy response in gastric cancer

BackgroundGastric cancer (GC) remains a significant health burden, calling for the discovery of novel biomarkers. Golgi apparatus, a crucial cellular organelle involved in tumorigenesis, remains underexplored in GC research. A comprehensive understanding of its role and associated mechanisms is urgently needed.Materials and methodsUtilizing the TCGA-STAD dataset as the training cohort and GSE84433 as the validation cohort, we explored potential associations between Golgi apparatus-related genes (GARG) and GC clinical risk. We aimed to decipher the prognostic significance and underlying biological mechanisms of these genes via consistent clustering, differential expression analysis, enrichment analyses, and immune infiltration profiling. To assess the relationship between risk stratification and survival outcomes, drug sensitivity, and immune infiltration, we developed the Golgi Apparatus-Related Risk Signature (GARRS). The reliability of GARRS was further corroborated using immunohistochemical staining.ResultsConsensus clustering based on 17 GARG identified two patient subgroups, C1 and C2, exhibiting differential survival, immune scores, and immune cell infiltration. We developed a GARRS using Cox-Lasso regression analysis, accurately stratifying patients into high- and low-risk groups. GARRS’ validity was confirmed in the validation set and immunohistochemical staining. Our findings underline the Golgi apparatus' significance in the GC immune microenvironment and GARRS' utility in predicting GC survival outcomes.ConclusionThis study underscores the association between Golgi apparatus subtypes and GC immunotumor microenvironment. GARRS, validated for its prognostic, immune infiltration, and drug sensitivity predictive abilities, offers new insights into gastric cancer treatment strategies.

Huaier inhibits the proliferation and migration of gastrointestinal stromal tumors by regulating the JAK2 / STAT3 signaling pathway.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract, often accompanied by a high risk of recurrence and drug resistance. Huaier (Trametes robiniophila Murr), a traditional Chinese medicinal fungus, has demonstrated potent anticancer properties and is widely used as an adjuvant treatment for liver, breast, gastric, colon, and non-small cell lung cancers. However, its effects and molecular mechanisms in GIST remain unclear. This study aims to explore the inhibitory effects and underlying mechanisms of Huaier on GIST through network pharmacology and experimental validation. Initially, we utilized a publicly accessible database to identify the core targets and principal pathways associated with Huaier's therapeutic effects on gastrointestinal stromal tumors. To further evaluate its biological impact, cell viability, proliferation, migration, and invasion were assessed through CCK-8 and EdU assays, wound healing tests, and Transwell experiments. Apoptotic cell death was quantified using flow cytometry analysis. Additionally, the influence of Huaier extract on the expression levels of JAK2 and STAT3 proteins was examined via Western blotting. Finally, a subcutaneous xenograft mouse model was employed to investigate the anti-tumor efficacy of Huaier in vivo. In this study, GAPDH, TNF, STAT3, ESR1, EGFR, IL6, CCND1, PTGS2, BCL2L1, and MAPK3 were identified as shared molecular targets, with the JAK/STAT signaling pathway recognized as the pivotal regulatory mechanism. Experimental findings demonstrated that Huaier exerted inhibitory effects on the proliferation, migration, and invasion of GIST-T1 and GIST-882 cells, exhibiting both dose- and time-dependent responses. Furthermore, Huaier was found to promote apoptosis in these cells. Western blot analysis revealed that treatment with Huaier extract significantly decreased the phosphorylation levels of JAK2 and STAT3, thereby suppressing the activation of the JAK2 / STAT3 signaling cascade. In vivo experiments further substantiated these findings, showing that Huaier treatment markedly reduced tumor size and inhibited tumor progression. Our results suggest that Huaier may inhibit the growth of GIST cells by inhibiting the JAK2/STAT3 signaling pathway, reduce cell proliferation, induce apoptosis, reduce cell migration and invasion, and show anti-tumor effects in vivo and in vitro.

Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway

Despite advances in gastric cancer diagnosis and treatment, its prognosis remains poor owing to aggressive tumor progression and metastasis. As understanding the relevant molecular mechanisms is essential to effectively improve patient outcomes, we elucidated the role of Kindlin-1 in gastric cancer progression and metastasis. Kindlin-1 expression was analyzed in 359 gastric cancer tissue samples provided by Kangnam Sacred Heart Hospital and publicly available GSE datasets. Kindlin-1 showed significantly higher expression in gastric cancer tissues than that in normal tissues, and high Kindlin-1 expression was associated with poor prognosis. Further, the mRNA and protein expression of Kindlin-1 were high in gastric cancer cell lines, where they were associated with increased proliferation, migration, and invasion. Our findings demonstrated that Kindlin-1 regulated epithelial–mesenchymal transition-related genes through interaction with activated Wnt/β-catenin signaling. Notably, Kindlin-1 enhanced β-catenin expression and promoted its nuclear translocation from the cytoplasm, increasing TCF4 transcriptional activity and inducing gastric cancer progression and metastasis. Overall, these findings demonstrate that Kindlin-1 is upregulated in gastric cancer and activates Wnt/β-catenin signaling to promote cell proliferation and motility.

Lidocaine Enhanced Antitumor Efficacy and Relieved Chemotherapy-Induced Hyperalgesia in Mice with Metastatic Gastric Cancer.

With the widespread use of lidocaine for pain control in cancer therapy, its antitumor activity has attracted considerable attention in recent years. This paper provides a simple strategy of combining lidocaine with chemotherapy drugs for cancer therapy, aiming to relieve chemotherapy-induced pain and achieve stronger antitumor efficacy. However, there is still a lack of substantial pre-clinical evidence for the efficacy and related mechanisms of such combinations, obstructing their potential clinical application. In this study, we propose intraperitoneal chemotherapy (IPC) against gastric cancer (GC) as an ideal scenario to evaluate the efficacy of a lidocaine/paclitaxel combination. Firstly, we used human GC cells MKN-45-luc to investigate the antitumor activity and related mechanisms of the lidocaine/paclitaxel combination in vitro. Then, we used C57BL/6 mice with intraperitoneal drug suffusion to evaluate the efficacy of lidocaine to suppress paclitaxel-induced hyperalgesia and related mechanisms. Lastly, in BALB/c tumor-bearing nude mice we evaluated the synergistic antitumor activity and pain-relieving effect of the lidocaine/paclitaxel combination. Our results showed enhanced antitumor activity for the lidocaine/paclitaxel combination, which induced apoptosis, inhibited migration, and the invasion of GC cells in a synergistic manner. In animal models, the lidocaine/paclitaxel combination effectively inhibited growth and peritoneal metastasis of the tumor, resulting in prolonged survival time. Meanwhile, lidocaine showed considerable anti-inflammatory activity alongside its anesthetic effect, which, in combination, effectively relieved hyperalgesia induced by paclitaxel. These results suggested that intraperitoneal suffusion with lidocaine/paclitaxel could be a pain-free IPC formulation with enhanced antitumor activity, which could provide a promising treatment for GC with peritoneal metastasis.

Association of Body Composition Parameters with the Short- and Long-Term Efficacy of Neoadjuvant Immunotherapy Combined with Chemotherapy in Advanced Gastric Cancer

Background Immunotherapy has become a prevalent strategy in the neoadjuvant treatment of advanced gastric cancer (AGC). This study investigates the predictive value of computed tomography (CT)-derived body composition parameters on the efficacy of neoadjuvant immunotherapy for AGC. Methods Data on 103 patients with resectable AGC who received neoadjuvant immunotherapy combined with chemotherapy at a teaching hospital between March 2020 and August 2022 were collected. Body composition parameters, including the subcutaneous adipose index (SAI), visceral adipose index (VAI), and skeletal muscle index (SMI), were calculated from pretreatment CT images. Logistic regression and Cox proportional hazards models assessed the impact of these parameters on pathological responses and survival outcomes following treatment. Results Of the patients, 34 (33.0%) achieved a major pathological response (MPR). Higher SAI, VAI, and SMI values were significantly linked to an increased likelihood of achieving MPR (p < 0.05). Multivariate regression analysis revealed that only SAI independently predicted MPR (OR 1.042, 95% CI 1.009–1.077, p = 0.013). Furthermore, patients with a high SAI had significantly improved 2-year overall survival (76.9% vs. 54.9%, log-rank p = 0.012) and 2-year event-free survival (71.2% vs. 51.0%, log-rank p = 0.022) compared to those with low SAI. The survival benefit associated with high SAI was partly due to its higher MPR rate (mediating proportion: 37.5%, 95% CI: 12%–110%). Conclusion Pretreatment SAI independently correlates with MPR and better oncological outcomes in patients with AGC receiving neoadjuvant immunotherapy.

Severe cutaneous drug toxicity following disitamab vedotin treatment for metastatic gastric cancer: a case report

BackgroundThis study reports a case of severe cutaneous toxicity in a patient with metastatic gastric cancer induced by disitamab vedotin, emphasizing the need for careful monitoring and management in such treatments.Case presentationA 71-year-old female was admitted to hospital complaining of serious rashes following the first cycle of disitamab vedotin regimen for metastatic gastric cancer. The doctor diagnosedtoxic epidermal necrolysis (TEN) induced by the drug. The patient received high-dose methylprednisolone due to the side effects. This resulted in a gradual improvement of symptoms.ConclusionDuring the use of disitamab vedotin, patients need to be monitored for severe skin toxicity.

Overexpression of miR‑424‑5p reduces cisplatin resistance by downregulating SMURF1 in gastric cancer.

Chemoresistance is a major obstacle in the treatment of gastric cancer (GC). Notably, aberrant expression of microRNAs (miRs) is closely related to tumor development and progression. In the present study, the role of miR-424-5p in the chemoresistance of GC was investigated. Reverse transcription-quantitative PCR was used to detect the expression levels of miR-424-5p in tissues and different cell lines. Cell viability and apoptosis were detected via a Cell Counting Kit-8 assay, western blotting and flow cytometry. The targeting relationship between miR-424-5p and SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1) was verified via dual-luciferase reporter assays and the molecular mechanism was investigated by western blotting. The results revealed that miR-424-5p was expressed at low levels in GC tissues and cell lines, and that low miR-424-5p expression was associated with poor N stage and worse prognosis, especially in patients who received adjuvant chemotherapy. Further experiments revealed that the overexpression of miR-424-5p reduced cisplatin (CDDP) resistance and promoted GC cell apoptosis, whereas inhibiting miR-424-5p had the opposite effect. Mechanistically, it was found that miR-424-5p downregulated the expression of SMURF1 to regulate the expression of ING2 and p53, thereby modulating CDDP resistance in GC. In summary, the present study demonstrated that miR-424-5p may serve an important regulatory role in CDDP resistance in GC, and could be a potential diagnostic biomarker and therapeutic target for GC chemoresistance.

Didymin Inhibits Proliferation and Induces Apoptosis in Gastric Cancer Cells by Modulating the PI3K/Akt Pathway

Gastric cancer (GC) is a malignant tumor with high morbidity and mortality rates worldwide. This study aimed to investigate the effects and mechanisms of action of didymin, a dietary flavonoid glycoside, on GC treatment. Human GC cell lines Hs-746T and AGS were used to assess the effects of didymin on cell viability, cell proliferation, and cell cycle. The results showed that didymin decreased the proliferative capacity of GC cells and blocked cell cycle. Didymin decreased wound healing, invasion, and migration capacities of GC cells. Mitochondrial reactive oxygen species (ROS) levels and mitochondrial membrane potentials were reduced in cells treated with didymin. Network pharmacology analysis revealed that the therapeutic effects of didymin on AGS cells were related to the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In vivo mouse xenograft studies confirmed that didymin treatment decreased tumor cell proliferation, cell cycle protein levels, and Akt phosphorylation. The present study demonstrated that didymin regulates mitochondrial function and the PI3K/Akt pathway to inhibit cell proliferation and induce apoptosis in GC cells in vitro and in vivo. Therefore, didymin is a promising drug for the treatment of GC.

Curcumin in gastric cancer treatment: A commentary on mechanistic insights and future directions.

The study by Yang et al presents a comprehensive investigation into the therapeutic potential of curcumin for gastric cancer (GC). Using network pharmacology, the researchers identified 48 curcumin-related genes, 31 of which overlap with GC targets. Key genes, including ESR1, EGFR, CYP3A4, MAPK14, CYP1A2, and CYP2B6, are linked to poor survival in GC patients. Molecular docking confirmed strong binding affinity of curcumin to these genes. In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823, suggesting its therapeutic potential in GC through multiple targets and pathways.

Effects of Shenqi Xiangyi granules in advanced gastric cancer chemotherapy.

Owing to the absence of specific symptoms in early-stage gastric cancer, most patients are diagnosed at intermediate or advanced stages. As a result, treatment often shifts from surgery to other therapies, with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment. To investigate both treatment efficacy and immune modulation. A total of 116 patients with advanced gastric cancer, admitted from January 2021 to December 2023, were selected and divided into two groups of 58 each using the random number table method. The control group received FOLFOX4 chemotherapy (oxaliplatin + calcium + folinate + 5-fluorouracil) combined with intravenous sindilizumab. The observation group received the same treatment as the control group, supplemented by oral administration of Senqi Shiyiwei granules. Both groups underwent treatment cycles of 3 weeks, with a minimum of two cycles. The therapeutic efficacy, immune mechanisms, and treatment-related toxicity and side effects were compared between the groups. The objective remission rate in the observation group (55.17%) was higher than that of the control group (36.21%) (P < 0.05). After two treatment cycle, CD3+, CD4+, and CD4+/CD8+ levels were higher in the observation group compared to the control group, while CD8+, regulatory T cells, and natural killer cells were lower (P < 0.05). Additionally, the incidence of leukopenia, nausea, and vomiting was lower in observed group (P < 0.05). No significant differences were observed in the incidence of other adverse reactions (P > 0.05). Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts, making it a valuable option in clinical treatment.

Comparison of the safety of esophagojejunal overlap and π-shaped anastomosis in totally laparoscopic total gastrectomy

BackgroundGlobally, totally laparoscopic total gastrectomy is increasingly being accepted by surgeons for the treatment of gastric cancer. Overlap anastomosis and π-shaped anastomosis are the two most commonly used anastomosis methods in total laparoscopic surgery; however, their safety and suitability for the population are still unclear.MethodsA total of 162 consecutive patients with gastric cancer who underwent total laparoscopic total gastrectomy with overlap or π-shaped anastomosis were retrospectively analyzed. The intraoperative conditions and postoperative complications were compared.ResultsA significant difference in the tumor location was found between the two groups (p < 0.05). No significant difference was found in the operation time, intraoperative blood loss, and postoperative hospital stay between the two anastomosis methods (p > 0.05); however, the π-shaped anastomosis group had more postoperative anastomotic leakage (p < 0.05).ConclusionsOverlap anastomosis is recommended as the preferred anastomosis for totally laparoscopic total gastrectomy, and π-shaped anastomosis can be applied to non-gastroesophageal junction cancer with lower tumor location.

Role of exosomal miRNAs and macrophage polarization in gastric cancer: A novel therapeutic strategy.

Gastric cancer (GC) is one of the most common gastrointestinal cancers worldwide, with consistently high morbidity and mortality rates and poor prognosis. Most patients are diagnosed at an advanced stage due to the lack of specific presentation in the early stages. Exosomes are a class of extracellular vesicles (EVs) widely found in body fluids and can release genetic material or multiple proteins to facilitate intercellular communication. In recent years, exosomal miRNAs have gained attention for their role in various cancers. These exosomal miRNAs can impact GC development and progression by targeting specific genes or influencing signaling pathways and cytokines involved in Angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and immune regulation. They show great potential in terms of diagnosis, prognosis, and treatment of GC. Notably, the gastrointestinal tract has the largest number of macrophages, which play a significant role in GC progression. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and can influence macrophage programming through various mediators, including macrophage polarization. Macrophage polarization is involved in inflammatory responses and significantly impacts the GC process.

Nomogram for pre-procedural prediction of lymph node metastasis in patients with submucosal early gastric cancer.

The treatment of early gastric cancer (EGC) is contingent upon the status of lymph node metastasis (LNM). Accurate preoperative prediction of LNM is critical for reducing unnecessary surgeries. This study seeks to evaluate the risk factors for LNM in submucosal EGC and develop a predictive model to optimize therapeutic decision-making. A retrospective analysis was performed on clinical data from 389 patients with T1b-stage EGC who underwent radical gastrectomy. Univariate and multivariate analyses were conducted to identify independent risk factors, followed by the development of a nomogram to predict LNM. The model's efficacy was validated through receiver operating characteristic curves, calibration curves, and decision curve analysis. Of the 389 patients, 77 had LNM. Logistic regression analysis identified gender, CA199 levels, tumor location, degree of differentiation, presence of ulcers, and lymph node enlargement on CT as independent risk factors for LNM. A nomogram was constructed to assess the risk of LNM, demonstrating strong predictive accuracy with an area under the curve of 0.82 in the training set and 0.74 in the validation set, along with good sensitivity and positive predictive value. This study presents a reliable preoperative nomogram to estimate the likelihood of LNM in submucosal EGC, providing valuable guidance for determining the most effective treatment strategies for patients.

The regulatory role of integrin in gastric cancer tumor microenvironment and drug resistance.

Gastric cancer (GC) remains a significant global health burden due to its high aggressiveness, early metastasis, and poor prognosis. Despite advances in chemotherapy and targeted therapies, drug resistance remains a major obstacle to improving patient outcomes. Integrins, a family of transmembrane receptors, play a pivotal role in mediating tumor growth, invasion, and drug resistance by interacting with the tumor microenvironment (TME) and regulating signaling pathways such as Wnt/β-catenin, FAK, and MAPK. This review highlights the critical functions of various integrin subunits (e.g., α5, αv, β1, β3, β6) in promoting GC progression and their involvement in chemoresistance mechanisms. Additionally, integrins modulate immune cell infiltration and stromal cell interactions within the TME, further complicating GC treatment. Emerging evidence suggests that targeting integrins, either through inhibitors or integrin-specific therapeutic strategies, holds potential in overcoming drug resistance and improving clinical outcomes. This review underscores the need for further exploration of integrins as therapeutic targets in GC and suggests promising avenues for integrin-based therapies in personalized medicine.