BACKGROUND: Focal liver lesions (FLLs) are a common form of liver disease, and identifying accurate pathological types is required to guide treatment and evaluate prognosis. PURPOSE: To compare and analyze the application effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in the clinical diagnosis of focal liver lesions. MATERIAL AND METHODS: A retrospective analysis was performed on 682 patients with space-occupying liver lesions admitted to our hospital between December 2015 and August 2021. Of these, 280 underwent CEUS-guided biopsies and 402 underwent conventional US biopsies, with the results of each biopsy subsequently compared between the two groups. The success rate and accuracy of the biopsies and their relationship with different pathological features were also analyzed. RESULTS: The success rate, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value of the CEUS group were significantly higher than those of the US group (P < 0.05). Lesion size accuracy in the CEUS group was significantly higher than that in the US group (89.29% vs. 40.55%; P < 0.05). Lesion type accuracy in the CEUS group was significantly higher than that in the US group (86.49% vs. 43.59%), and the difference between the two groups was statistically significant (P < 0.05). The logistic regression analysis indicated that malignant lesions, lesions ≥5 cm, and lesions ≤1 cm were independent factors affecting the success rate of the puncture procedure (P < 0.05). CONCLUSION: The sensitivity, specificity, and diagnostic accuracy of lesion size and type in the CEUS group were higher than those in the US group.
BACKGROUND: The incidence of gastric cancer has significantly increased in recent years. Surgical resection is the main treatment, but the method of digestive tract reconstruction after gastric cancer surgery remains controversial. In the current study, we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after surgery. To this end, we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction (DTR) and esophageal jejunum Roux-en-Y reconstruction (RY). AIM: To explore the application effect of DTR in total laparoscopic radical total gastrectomy (TLTG) and evaluate its safety and efficacy. METHODS: We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January 2023. Among them, 35 cases were treated with DTR, and the remaining 42 cases were treated with traditional RY. After 1:1 propensity score matching, the cases were grouped into 31 cases per group, with evenly distributed data. The clinical characteristics and short- and long-term clinical outcomes of the two groups were statistically analyzed. RESULTS: The two groups showed no significant differences in basic data, intraoperative blood loss, number of lymph node dissections, first defecation time after operation, postoperative hospital stay, postoperative complications, and laboratory examination results on the 1st, 3rd, and 5th days after operation. The operation time of the DTR group was longer than that of the RY group [(307.58 ± 65.14) min vs (272.45 ± 62.09) min, P = 0.016], but the first intake of liquid food in the DTR group was shorter than that in the RY group [(4.45 ± 1.18) d vs (6.0 ± 5.18) d, P = 0.028]. The incidence of reflux heartburn (Visick grade) and postoperative gallbladder disease in the DTR group was lower than that in the RY group (P = 0.033 and P = 0.038). Although there was no significant difference in body weight, hemoglobin, prealbumin, and albumin between the two groups at 1,3 and 6 months after surgery, the diet of patients in the DTR group was better than that in the RY group (P = 0.031). CONCLUSION: The clinical effect of DTR in TLTG is better than that of RY, indicating that it is a more valuable digestive tract reconstruction method in laparoscopic gastric cancer surgery.
BACKGROUND: Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. METHOD: The data were extracted from the Fourth Hospital of Hebei Medical University's (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann-Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. RESULTS: Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241). CONCLUSION: The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.
Mitoxantrone Hydrochloride Injection for Tracing (MHI), a modified new drug marketed in China, has been approved by the National Medical Products Administration for lymph node tracing in thyroid cancer and sentinel lymph node biopsy in breast cancer. This single-center, single-blind, dose-escalation phase I clinical trial aimed to investigate the safety of MHI on lymph node tracing in gastric cancer. In this study, four dose groups (1.0 mL, 1.5 mL, 2.0 mL, and 3.0 mL) with 3 gastric cancer patients in each group were set. The safety, tolerability, pharmacokinetics and preliminary efficacy of different doses were investigated. Results showed that none of the patients experienced dose-limiting toxicity or developed serious adverse events or adverse drug reactions. Pharmacokinetic analyses revealed minimal absorption of the tracer, resulting in low and transient blood drug concentrations across all participants. The mean time to peak concentration was (0.561 ± 0.3728) h (with mean peak concentration (Cmax) of 10.300 ng/mL), (0.500 ± 0.0167) h (mean Cmax of 13.687 ng/mL), (0.494 ± 0.0096) h (mean Cmax of 30.933 ng/mL), and (0.661 ± 0.2791) h (mean Cmax of 21.067 ng/mL) in the 1.0 mL, 1.5 mL, 2.0 mL, and 3.0 mL dose groups, respectively. The mean lymph node staining rates were 21.0%, 24.7%, 32.5%, and 44.5%, and the mean metastatic lymph node staining rates were 20.6%, 36.1%, 42.4%, and 21.0% in each group. This study confirmed that MHI was safe, well-tolerated, and had low systemic effects when used for lymphatic tracing of gastric cancer, and the tracing effect was better in the 3 mL dose group. This trail was registered on the website of Centre for Drug Evaluation State Drug and Food Administration (http://www.chinadrugtrials.org.cn/index.html) with the name of clinical study of lymphatic tracer in lymph node tracing of gastric cancer, the code was CTR20201906.
BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.
BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths worldwide. Prognostic assessments are typically based on the tumor-node-metastasis (TNM) staging system, which does not account for the molecular heterogeneity of this disease. LATS2, a tumor suppressor gene involved in the Hippo signaling pathway, has been identified as a potential prognostic biomarker in gastric cancer. AIM: To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following radical surgery, and compare its predictive performance with traditional TNM staging. METHODS: A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted. The patients were divided into a training group (171 patients) and a validation group (74 patients) to develop and test our prognostic model. The performance of the model was determined using C-indices, receiver operating characteristic curves, calibration plots, and decision curves. RESULTS: The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set. Area under the curve values for three-year and five-year survival prediction were significantly robust, suggesting an excellent discrimination ability. Calibration plots confirmed the high concordance between the predictions and actual survival outcomes. CONCLUSION: We developed a nomogram model incorporating LATS2 expression, which significantly outperformed conventional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery. This model may serve as a valuable tool for individualized patient management, allowing for more accurate stratification and improved clinical outcomes. Further validation in larger patient cohorts will be necessary to establish its generalizability and clinical utility.
Gastric cancer (GC) is difficult to characterize due to its heterogeneity, and the complicated heterogeneity leads to the difficulty of precisely targeted therapy. The spatially heterogeneous composition plays a crucial role in GC onset, progression, treatment efficacy, and drug resistance. In recent years, the technological advancements in spatial omics has shifted our understanding of the tumor microenvironment (TME) from cancer-centered model to a dynamic and variant whole. In this review, we concentrated on the spatial heterogeneity within the primary lesions and between the primary and metastatic lesions of GC through the TME heterogeneity including the tertiary lymphoid structures (TLSs), the uniquely spatial organization. Meanwhile, the immune phenotype based on spatial distribution was also outlined. Furthermore, we recapitulated the clinical treatment in mediating spatial heterogeneity in GC, hoping to provide a systematic view of how spatial information could be integrated into anti-cancer immunity.
Stomach Neoplasms , Tertiary Lymphoid Structures , Humans , Tumor Microenvironment , Stomach Neoplasms/genetics , Phenotype
BACKGROUND: Microvascular invasion (MVI) is an important predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy. Shear wave elastography (SWE) plays an important role in hepatic imaging, but its value in the preoperative prediction of MVI in HCC has not yet been proven. AIM: To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC. METHODS: Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study. Conventional ultrasound features and SWE features such as maximal elasticity (Emax) of HCCs and Emax of the periphery of HCCs were acquired before surgery. These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs. RESULTS: This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs, including 54 with mild MVI and 48 with severe MVI. Maximal tumor diameters, surrounding liver tissue, color Doppler flow, Emax of HCCs, and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs. In addition, Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs. Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI, with odds ratios of 2.820 and 1.021, respectively. CONCLUSION: HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI. Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.
Long noncoding RNA (lncRNA) plays crucial roles in the development of gastric cancer (GC); however, studies of their mechanisms of action are needed to determine their clinical value. The aim of this study is to explore the effects and mechanisms of THUMPD3-AS1 in GC. Elevated levels of THUMPD3-AS1 were observed in GC and demonstrated a significant positive correlation with poor prognosis. Functionally, THUMPD3-AS1 promoted GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and induced tumor growth in vivo. THUMPD3-AS1 exerts its regulatory function on BCAT1 through competitive binding with miR-1297. Further investigations confirmed that both THUMPD3-AS1 and miR-1297 interact with BCAT1. These findings suggest that THUMPD3-AS1 promotes GC invasion and EMT by regulating the miR-1297/BCAT1 pathway, indicating that THUMPD3-AS1 may serve as a biomarker and therapeutic target for GC.
BACKGROUND: Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone. MATERIALS AND METHODS: Three hundred patients younger than 60 years with potentially resectable advanced gastric cancer (cT3-4, Nany, M0) were enrolled in this randomized controlled clinical trial between November 2014 and June 2018. The primary endpoint of the study was the pathological complete response (pCR) rate. Secondary endpoints included 3-year overall survival (OS), 3-year disease-free survival. RESULTS: In total, 280 patients (93 in the DOX group, 92 in the XELOX group, and 95 in the surgery group) were included in the per-protocol analysis. The DOX group demonstrated a significantly higher pCR rate compared to the XELOX group (16.1 vs. 4.3%, P =0.008). For patients with intestinal type, the DOX group exhibited significantly higher rates of both pCR and major pathological response compared to the XELOX group ( P =0.007, P <0.001). The 3-year OS rates of the DOX group, the XELOX group and the surgery group were 56.9, 44.6, and 34.7%, respectively. The 3-year disease-free survival rates were 45.2, 40.2, and 28.4%, respectively. The neoadjuvant DOX regimen demonstrated a significant improvement in the 3-year OS of patients compared to the neoadjuvant XELOX regimen ( P =0.037). CONCLUSION: The neoadjuvant DOX regimen has shown the potential to increase the pCR rate and improve the prognosis of patients with advanced gastric cancer who are under 60 years old.
Adenocarcinoma , Stomach Neoplasms , Humans , Middle Aged , Capecitabine/therapeutic use , Stomach Neoplasms/surgery , Docetaxel/therapeutic use , Neoadjuvant Therapy , Oxaliplatin/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adenocarcinoma/surgery , Fluorouracil
[This corrects the article DOI: 10.1016/j.isci.2023.107673.].
Introduction: Neutrophils are important immune cells in the body, extremely abundant, phagocytic and bactericidal, and usually involved in the defense against infectious diseases as immune become. However, a new reticulum structure has been discovered: neutrophil extracellular traps (NETs), which consists of various components such as DNA and proteins, etc. Current studies have found that NETs are closely associated with various diseases such as immune diseases, inflammation and tumors, and the study of the development and metastasis of gastrointestinal tumors has become a recent research hotspot. The clinical significance of NETs has been gradually highlighted, especially in the area of immunosuppression. Methods: We reviewed a large amount of relevant literature, summarized the latest detection methods of NETs, explored the mechanism of NETs in gastrointestinal tumors and summarized the latest hotspot directions. Results: NETs are involved in the development of gastrointestinal tumors, and are closely related to the proliferation and metastasis of gastrointestinal tumors. Higher levels of NETs are associated with poor prognosis of gastrointestinal tumors, promote local growth of tumors through various pathways, participate in tumor-related systemic injury, and promote tumor growth and metastasis by enhancing the mitochondrial function of tumor cells and awakening dormant tumor cells. Discussion: NETs are highly expressed in tumors, and tumors and their microenvironment can promote the production of NETs, providing new ideas for the clinical diagnosis and treatment of gastrointestinal tumors. In this paper, we describe the basic information about NETs, explore the research mechanisms related to NETs in gastrointestinal tumors, and prospectively explore the clinical potential of hotspots and inhibitors related to NETs for gastrointestinal tumors, in order to provide new ideas and targets for the diagnosis and treatment of gastrointestinal tumors.
BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.
Carcinoma , Stomach Neoplasms , Humans , Lymphatic Metastasis , Retrospective Studies , Dietary Supplements
Objective: To investigate the survival and independent prognostic factors for single large hepatocellular carcinoma (SLHCC) after surgical resection. Methods: Patients with SLHCC who underwent radical resection from January 2013 to December 2017 were retrospectively analyzed. The Kaplan-Meier method was used to analyze the overall survival (OS) rate and recurrence-free survival (RFS) rates. Cox forward stepwise regression was performed to analyze the independent prognostic factors. Results: A total of 485 cases were included. The average age was 51.2±11.2 years, 88.9% had a history of hepatitis B virus infection, and most patients had normal liver function. The average tumor diameter was 8.8±3.0 cm. The 1-, 3-, and 5-year OS and RFS rates were 76.8%, 56.7%, and 45.7%, and 61.0%, 46.2%, and 34.7%, respectively. Multivariate analysis showed that liver cirrhosis (HR=1.456, P=0.004), total bilirubin (TB) ≥17.1 µmol/L (HR=1.437, P=0.011), glutamyl transferase (GGT) >60 U/L (HR=1.438, P=0.020), lactate dehydrogenase (LDH) >225 U/L (HR=1.442, P=0.007), blood loss ≥400 mL (HR=1.339, P=0.027), microvascular invasion (MVI) (HR=1.492, P=0.004), satellite lesions (HR=1.859, P<0.0001) and Edmondson-Steiner grade III+IV (HR=1.740, P=0.018) were independent risk factors for reduced OS in SLHCC patients. Sex (HR=1.763, P=0.003), liver cirrhosis (HR=1.382, P=0.007), GGT >60 U/L (HR=1.512, P=0.003), LDH >225 U/L (HR=1.480, P=0.002), MVI (HR=1.545, P=0.001), and satellite lesions (HR=1.564, P=0.001) were independent risk factors for reduced RFS. OS and RFS nomograms were constructed using risk factors with C-index values of 0.692 (95% CI: 0.659-0.724) and 0.659 (95% CI: 0.623-0.693), respectively. The Hosmer-Leme test demonstrated the good fit of both nomograms. Conclusion: Surgical resection is the standard and effective treatment for SLHCC patients. Sex, liver cirrhosis, TB≥17.1 µmol/L, GGT>60 U/L, LDH>225 U/L, blood loss≥400 mL, MVI, Edmondson-Steiner grade III+IV, and satellite lesions were found to be independent prognostic factors in SLHCC patients following radical resection. The OS and RFS nomograms accurately predicted the prognosis of SLHCC patients.
Ferroptosis is a novel cell death modality discovered in recent years that is different from apoptosis and necrosis. It is usually associated with changes in the regulatory signaling in multiple organelles and depends on iron. It is caused by an imbalance between the generation and degradation of intracellular lipid reactive oxygen species (ROS). In addition to increased levels of cytoplasmic ROS and lipids, decreased mitochondrial volume and thickened mitochondrial membranes are markers of ferroptotic death. Gastric cancer is a common malignant tumor, but few studies on the possible role of ferroptosis in gastric cancer have been reported. Although ferroptosis is involved in multifactor-induced carcinogenesis, studies have also shown the role of ferroptosis in the selective killing of tumor cells, thereby inhibiting tumor progression and metastasis. In this paper, the definition, characteristics, and regulatory mechanism of ferroptosis and its potential role in gastric cancer are discussed. Therefore, this review is expected to provide a reference for the treatment of diseases based on ferroptosis and provide a direction for future research on the pathogenesis and development of gastric cancer and the development of anticancer drugs.
Ferroptosis , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Reactive Oxygen Species/metabolism , Apoptosis , Cell Death
BACKGROUND: The Asian Cancer Research Group (ACRG) classification is a molecular classification established based on the tissues of gastric cancer (GC) patients in Asia. Patients with different ACRG subtypes differ significantly with regard to treatment response and prognosis, which indicates that the ACRG molecular classification is more valuable than the traditional pathological classification. However, the specific differentially expressed genes (DEGs) and the value of the ACRG molecular subtypes of GC have not been studied in depth. METHODS: Through the analysis of the GEO database, the DEGs in GC tissues of different ACRG molecular subtypes were investigated. The expression and mechanism of the screened angiotensin II receptor type 1 (AGTR1) gene were bioinformatically analyzed and experimentally verified. The role of AGTR1 in GC cells was mainly investigated using CCK-8, wound-healing, transwell invasion assays, qRT-PCR, and Western blotting. RESULTS: The bioinformatics results showed the presence of multiple DEGs in GC tissues with different ACRG molecular subtypes. Certain DEGs in GC tissues of different ACRG molecular subtypes have prognostic significance. AGTR1 levels in tumor tissues were significantly higher than in paired paracancerous tissues. The prognosis of GC patients with high expression of AGTR1 was poor (p < 0.05). The AGTR1 gene in GC samples was associated with the expression of immune pathways and immune checkpoint genes. After modifying AGTR1 expression in cell lines, cells' proliferation, invasion, and migration abilities and the expression of related genes changed. CONCLUSIONS: There were significant DEGs in GC tissues with different ACGR molecular types, among which the increased expression of AGTR1 was a molecular feature of MSS/EMT type gastric cancer. Further study found that AGTR1 was closely related to tumor immune infiltration and invasion and may be a new therapeutic target gene for gastric cancer.
Gastric cancer (GC) remains one of the most common malignancies worldwide. Despite immune-checkpoint inhibitors (ICIs) has revolutionized cancer treatment and obtained durable clinical responses, only a fraction of GC patients benefit from it. As an important component of T cells, regulatory T cells (Tregs) play a vital role in the pathogenesis of GC, keep a core balance between immune suppression and autoimmunity, and function as predictive biomarkers for prognosis of GC patients. In this review, we discuss the role of Tregs in the pathogenesis of GC, and targeting Tregs via influencing their transcription factor, migration, co-stimulatory receptors, immune checkpoints, and cytokines. We also focus on the currently important findings of Tregs metabolism including amino acid, fatty acid, and lactic acid metabolism of GC. The emerging role of microbiome and clinical combined therapy in modulating Tregs in GC treatment is also summarized. Meanwhile, this review recapitulates a novel regulator, magnesium, is involved in mediating Tregs in GC. These research advances on Treg-related strategies provide new insights and challenges for GC progression, treatment, and prognosis. And we hope our review can stimulate further discovery and implication of mediators and pathways targeting Tregs.
Stomach Neoplasms , T-Lymphocytes, Regulatory , Humans , Stomach Neoplasms/drug therapy , Immunotherapy , Immunosuppression Therapy , Autoimmunity
Objective: To analyze the recurrence and metastasis patterns and prognosis after complete resection of retroperitoneal liposarcoma. Methods: The clinical postoperative follow-up data and results of patients who underwent complete resection of retroperitoneal liposarcoma from September 10, 2014, to September 8, 2021, at Hebei Medical University hospital were collected retrospectively. Results: A total of 60 patients with complete resection of retroperitoneal liposarcoma, including 33 cases of retroperitoneal liposarcoma recurrence, 2 cases of liver metastasis, and 1 case of lung metastasis, were included. The results showed that 100% of the recurrent sites were located in the primary region of the tumor, with most recurrences located near the kidney, paracolic sulci, and iliac vessels. Three patients had distant metastasis without obvious recurrence on imaging examination. The pathological type of retroperitoneal liposarcoma, Ki67 expression, and presence of serum albumin were risk factors for recurrence and metastasis after complete resection of retroperitoneal liposarcoma. The malignancy and Ki67 expression were independent risk factors for recurrence and metastasis as well as for overall survival of patients undergoing complete resection of retroperitoneal liposarcoma. Conclusion: Complete resection remains the most effective method to treat retroperitoneal liposarcoma. Patients with pathological types of retroperitoneal liposarcoma showing dedifferentiation, pleomorphism, mixed type, and high Ki67 expression should be closely monitored and observed after complete resection, especially for imaging changes in the primary tumor area.
Background: Targeted therapy with tyrosine kinase inhibitors (TKIs) benefits most patients with stromal tumors; however, the effects of TKIs in patients with rare cases of gastrointestinal stromal tumors (GISTs) with platelet-derived growth factor receptor alpha (PDGFRA) exon 12 mutations are unclear. Our report of a case treated with multiline TKIs (included ripretinib) may provide some experience into the future management of rare GIST with PDGFRA 12 exon mutation. Case Description: We report the case of a patient (42-year-old female) with a PDGFRA exon 12-mutated GIST who underwent multiple surgeries and multiple lines of TKI therapy. This patient had intra-abdominal recurrence after imatinib, which was used as the 1st-line targeted drug treatment for 7 months after radical surgery, and had widespread metastases in the abdominal cavity after sunitinib, which was used as the 2nd-line targeted drug treatment for 6 months after the second radical surgery. For this advanced GIST patient with extensive intraperitoneal metastasis and rare PDGFRA 12 exon mutation, we then selected ripretinib as the 3rd-line targeted drug therapy to treat the patient. Up to the last follow-up in September 2021, the patient continued to take drugs without obvious complaints of discomfort or adverse events. Conclusions: This case showed that patients with PDGFRA exon 12-mutated GISTs are less likely to benefit from current conventional TKIs, and ripretinib treatment should be considered preferred to regorafenib or even sunitinib according to each patient's situation. However, the limitation of our case is that the patient's second recurrent lesion was not genetically tested to determine the presence of secondary mutation. Further, if a patient's tumor has a high risk of adverse biological behaviors, such as high mitotic figures, vascular tumor thrombus, succinate dehydrogenase B (SDHB) was negative, and regional lymph node metastasis, consideration should be given to shortening the postoperative follow-up interval to 2 months or even 1 month.
Gastric cancer (GC) is one of the most common malignant tumors. Although there are multiple therapeutic methods, the 5-year survival rate for GC remains low primarily due to metastasis and resistance to chemotherapy. GC treatments, which include chemotherapy drugs, targeted drugs, and immunologic drugs, improve the prognosis of advanced GC patients. Nevertheless, resistance to these drugs may result in treatment failure. Tumor metastasis also plays a key role in tumor progression and limits the clinical efficacy of treatments. Recently, it has been reported that circular RNAs (circRNAs), non-coding RNAs, regulate GC drug resistance and metastasis to improve prognosis. In this review, we summarized systematically the underlying mechanisms of circRNA regulation of gastric neoplasm drug resistance and tumor metastasis. Thus we shed light on the potential of circRNAs to function as potential GC biomarkers and therapeutics.
