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OBJECTIVE: To systematically evaluate the efficacy and safety of radiofrequency ablation and liver resection in the therapeutic management of early-stage hepatocellular carcinoma. METHOD: We conducted a comprehensive search of domestic and foreign databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang to retrieve literature on radiofrequency ablation and liver resection for the treatment of early hepatocellular carcinoma. The retrieved literature underwent thorough screening, and relevant data were extracted. Following the evaluation of the literature's quality, Meta-analysis was performed using RevMan 5.4 software. RESULTS: In this study, a total of 11 documents were selected, comprising 1334 patients with hepatocellular carcinoma. Meta-analysis results indicated that there was no statistically significant difference in the 1-year overall survival rate [Relative risk (RR) = 1.01, 95% confidence intervals (CI) (0.98; 1.04)] and the 3-year overall survival rate [RR = 0.95, 95% CI (0.90; 1.01)] between the radiofrequency ablation and liver resection groups (p > 0.05). Similarly, there was no statistically significant difference in the 1-year disease-free survival rate [RR = 0.94, 95% CI (0.87; 1.01)] between the two groups. However, the 3-year disease-free survival rate [RR = 0.84, 95% CI (0.74; 0.96)] of patients in the radiofrequency ablation group was significantly lower than that in the hepatectomy group (p < 0.05). Notably, the incidence of complications [RR = 0.42, 95% CI (0.33; 0.55)] was significantly lower in the radiofrequency ablation group compared to the hepatectomy group. Conversely, the local recurrence rate [RR = 1.45, 95% CI (1.22; 1.73)] was significantly higher in the radiofrequency ablation group compared to the hepatectomy group (p < 0.05). CONCLUSION: During the treatment of hepatocellular carcinoma, hepatectomy demonstrates superior clinical efficacy compared to radiofrequency ablation, particularly in its ability to control tumor recurrence. However, radiofrequency ablation presents with fewer complications and a higher level of safety. These findings can serve as a valuable foundation for clinicians when selecting the most suitable treatment approaches for liver cancer.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Humanos , Hepatectomía/métodos , Ablación por Radiofrecuencia/métodos , Resultado del Tratamiento , Estadificación de Neoplasias , Tasa de Supervivencia , Ablación por Catéter/métodos , Supervivencia sin EnfermedadRESUMEN
Multiport robots are now widely used for total gastrectomy for gastric cancer, while there is almost a void of research on whether single-port (SP) robots can be used for total gastrectomy. Here, we report a case of a 75-year-old female patient who was diagnosed with gastric cardia adenocarcinoma by gastroscopy and underwent total gastrectomy assisted by the SHURUI SP robot. We successfully accomplished total gastrectomy and D2 lymph node dissection using the novel SP robotic platform. The patient was discharged from the hospital successfully with no complications during or after the surgery. Pathologic diagnosis showed adenocarcinoma of the gastric mucosa with partial signet-ring cell carcinoma, and no metastasis was found in the 29 cleared lymph nodes. The use of the SHURUI SP robot for total gastrectomy in treating gastric cancer is both technically feasible and safe.
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Adenocarcinoma , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias Gástricas , Femenino , Humanos , Anciano , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Escisión del Ganglio Linfático , Gastrectomía , Adenocarcinoma/cirugía , Adenocarcinoma/patologíaRESUMEN
Background: Hepatocellular carcinoma is a major contributor to cancer-related deaths in China and ranks among the most prevalent malignant tumors. . The study aimed to assess the efficacy and adverse reactions of transcatheter arterial chemoembolization combined with apatinib in treating hepatocellular carcinoma with portal vein tumor thrombus. Methods: When treating hepatocellular carcinoma with a portal vein tumor thrombus, the computer retrieves eight databases to find controlled trials on the effects of transcatheter arterial chemoembolization combined with apatinib. The Cochrane Library, WanFang databases EMbase, PubMed, Web of Science, China Biomedical Literature Database (CBM), & CNKI are all retrieved by the computer. "Transcatheter arterial chemoembolization", "apatinib", & "hepatocellular carcinoma" are the search terms. As this a meta-analysis, Utilizing RevMan 5.3 software, data analysis was carried out following a thorough assessment of the quality of the literature. Results: This meta-analysis finally contained 7 papers. According to a meta-analysis, the disease control rate of the test category was considerably greater than that of the control category (odd Ratio OR: 1.65; 95% Cl: 1.17,2.33; P = .01). The experimental cohort's level of VEGF was substantially lower than that of the control group (standardized mean difference SMD:-25.38; 95% Cl: -28.69,-21.79; P < .01). According to a meta-analysis, caspase-8 levels in the group that underwent the experiment were substantially greater than those in the control category (SMD: 15.12; 95% Cl: 12.09, 18.15; P < .01). The test control experienced considerably less pain than the control sample (OR: 0.86; 95% Cl: 0.75,0.99; P = .033). Conclusion: The findings of this trial indicate that individuals with HCC & PVTT may benefit from TACE & apatinib together, as evidenced by disease control rate, VEGF, Caspase-8, pain, hypertension, nausea and vomiting, and more reputable studies are required to support the aforementioned conclusions.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Trombosis , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Caspasa 8 , Factor A de Crecimiento Endotelial Vascular , Quimioembolización Terapéutica/efectos adversos , Resultado del Tratamiento , Trombosis/terapia , DolorRESUMEN
Background: To compare the perioperative and short-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) in recurrent hepatocellular carcinoma (rHCC) based on propensity score matching (PSM) to investigate therapeutic safety, efficacy, and value for clinical application. Methods: Forty-nine patients with rHCC who underwent surgery at Wenzhou People's Hospital between January 2017 and March 2022 were retrospectively analyzed and classified into LLR (n=30) and OLR (n=22) cases based on the surgical method. Thirty-eight patients were screened using PSM for data analysis to compare basic clinical characteristics, perioperative outcomes, and postoperative recurrence in both groups. Results: Before PSM, the tumour diameter was larger, tumor staging (BCLC staging system), intraoperative blood loss, units of blood transfused, constituent ratio of liver cirrhosis, incidence of MVI and intravascular tumour thrombus and postoperative complication were higher, and duration of hospital stay was significantly longer in the OLR group compared to those in the LLR group (p < 0.05). After PSM, there were no significant differences regarding tumour diameter, MVI incidence, blood transfusion amount or postoperative complication rate in the LLR and OLR groups. The tumor staging, incidence of vascular cancer thrombus, intraoperative blood loss and postoperative duration of hospitalisation were significantly higher in the OLR group than in the LLR group (p<0.05). The difference in recurrence-free survival (RFS) between the two groups was not statistically significant (p = 0.383). Conclusion: LLR for recurrent hepatocellular carcinoma can reduce intraoperative blood loss and postoperative complication rate, shorten the duration of hospitalisation, and is superior to OLR regarding perioperative and short-term efficacy, demonstrating good safety and feasibility.
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Background: Peritoneal dissemination (PD) is the most common mode of metastasis for advanced gastric cancer (GC) with poor prognosis. It is of great significance to accurately predict preoperative PD and develop optimal treatment strategies for GC patients. Our study assessed the diagnostic potential of serum tumor markers and clinicopathologic features, to improve the accuracy of predicting the presence of PD in GC patients. Methods: In our study, 1264 patients with GC at Fudan University Shanghai Cancer Center and Wenzhou people's hospital from 2018 to 2020 were retrospectively analyzed, including 316 cases of PD and 948 cases without PD. All patients underwent enhanced CT scan or magnetic resonance imaging (MRI) before surgery and treatment. Clinicopathological features, including tumor diameter and tumor stage (depth of tumor invasion, nearby lymph node metastasis and distant metastasis), were obtained by imaging examination. The independent risk factors for PD were screened through univariate and multivariate logistic regression analyses, and the results were expressed with 95% confidence intervals (CIs). A model of PD diagnosis and prediction was established by using Cox proportional hazards regression model of training set. Furthermore, the accuracy of the prediction model was verified by ROC curve and calibration plots. Results: Univariate analysis showed that PD in GC was significantly related to tumor diameter (odds ratio (OR)=12.06, p<0.0006), depth of invasion (OR=14.55, p<0.0001), lymph node metastases (OR=5.89, p<0.0001), carcinoembryonic antigen (CEA) (OR=2.50, p<0.0001), CA125 (OR=11.46, p<0.0001), CA72-4 (OR=4.09, p<0.0001), CA19-9 (OR=2.74, p<0.0001), CA50 (OR=5.20, p<0.0001) and CA242 (OR=3.83, p<0.0001). Multivariate analysis revealed that clinical invasion depth and serum marker of CA125 and CA72-4 were independent risk factors for PD. The prediction model was established based on the risk factors using the R program. The area under the curve (AUC) of the receiver operating characteristics (ROC) was 0.931 (95% CI: 0.900-0.960), with the accuracy, sensitivity and specificity values of 90.5%, 86.2% and 82.2%, respectively. Conclusion: The nomogram model constructed using CA125, CA72-4 and depth of invasion increases the accuracy and sensitivity in predicting the incidence of PD in GC patients and can be used as an important tool for preoperative diagnosis.
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Introduction: Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains to be elucidated. Objectives: Our study intended to identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC). Methods: Differentially expressed lncRNAs were determined by microarray analysis between GC cells exposed to hypoxia (1% O2) and normoxia (21% O2) for 24 h. The expression level of CBSLR was manipulated in several GC cell lines to perform molecular and biological analyses both in vitro and in vivo. Results: We identified a hypoxia-induced lncRNA-CBSLR that protected GC cells from ferroptosis, leading to chem-resistance. Mechanically, CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Notably, CBSLR is upregulated, whereas CBS is downregulated in GC tissues compared to matched normal tissues; and GC patients with high CBSLR/low CBS levels have a worse clinical outcome and a poorer response to chemotherapy. Conclusion: Our study reveals a novel mechanism in how HIF1α/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.
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Ferroptosis , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Hipoxia , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Ferroptosis, a unique form of nonapoptotic-regulated cell death caused by overwhelming lipid peroxidation, represents an emerging tumor suppression mechanism. Growing evidence has demonstrated that cell metabolism plays an important role in the regulation of ferroptosis. Specifically, the association between methionine metabolism and ferroptosis remains undefined. METHODS: We performed in vitro and in vivo experiments to evaluate the influence of methionine metabolism on ferroptosis sensitivity. Pharmacological and genetic blockade of the methionine cycle was utilized and relevant molecular analyses were performed. RESULTS: We identified MAT2A as a driver of ferroptosis resistance. Mechanistically, MAT2A mediates the production of S-adenosylmethionine (SAM), which upregulates ACSL3 by increasing the trimethylation of lysine-4 on histone H3 (H3K4me3) at the promoter area, resulting in ferroptosis resistance. CONCLUSIONS: Collectively, these results established a link between methionine cycle activity and ferroptosis vulnerability in gastric cancer.
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Coenzima A Ligasas , Ferroptosis , Metionina Adenosiltransferasa , Neoplasias Gástricas , Coenzima A Ligasas/genética , Ferroptosis/genética , Humanos , Metionina Adenosiltransferasa/genética , Regiones Promotoras Genéticas , S-Adenosilmetionina/metabolismo , Neoplasias Gástricas/genéticaRESUMEN
Prostate cancer (PCa) endangers the life and health of older men. Most PCa cases develop into castrationresistant PCa (CRPC) within 2 years. At present, the molecular mechanisms of the occurrence and development of PCa and its transformation to CRPC remain unknown. The present study aimed to investigate the role of CKLFlike Marvel transmembrane domain containing family member 5 (CMTM5) in PCa and its molecular mechanism in vitro. PCa tissues and paired adjacent normal prostate tissues from 70 patients were collected to examine the expression levels of CMTM5 and EGFR via immunohistochemistry, reverse transcriptionquantitative PCR and western blotting. Then, CMTM5overexpressing DU145 cells were constructed, and CMTM5 expression in these transfected cells and vector control cells was examined via western blotting. Cell Counting Kit8 and plate clone formation assays were used to evaluate the proliferation and colony number of CMTM5overexpressing cells and vector control cells. Then, cell migration and invasion were assessed using wound healing assay, Transwell assay and immunofluorescence analysis with DAPI staining. The effect of CMTM5 on apoptosis and its underlying molecular mechanism were examined using western blotting and flow cytometry. The results demonstrated that CMTM5 expression in PCa tissues and cell lines was significantly downregulated, while EFGR expression was significantly upregulated. The proportion of high CMTM5 expression in PCa tissues was significantly lower compared with that in normal prostate tissues. By contrast, the proportion of high EGFR expression in PCa tissues was significantly increased compared with that in normal prostate tissues. Moreover, CMTM5 overexpression significantly inhibited cell proliferation, migration and invasion, and promoted cell apoptosis compared with vector control cells in vitro. Furthermore, the regulation of PCa by CMTM5 was associated with the downregulation of PI3K/AKT and its downstream Bcl2 expression, as well as the upregulation of Bax expression. In conclusion, CMTM5 may be an effective tumor suppressor gene for PCa, especially for castrationresistant PCa, by downregulating EGFR and PI3K/AKT signaling pathway components.
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Quimiocinas/farmacología , Receptores ErbB/metabolismo , Proteínas con Dominio MARVEL/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Proteínas con Dominio MARVEL/genética , Proteínas con Dominio MARVEL/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Supresoras de Tumor/genética , Regulación hacia Arriba , Cicatrización de HeridasRESUMEN
BACKGROUND: Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. METHODS: A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. RESULTS: Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. CONCLUSION: Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatectomía/efectos adversos , Humanos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS: Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS: Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.
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Carcinoma Hepatocelular/patología , Diabetes Mellitus Tipo 2/epidemiología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/patología , Microvasos/patología , Adulto , Anciano , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/cirugía , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Occurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR). METHODS: Patients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method. RESULTS: This study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001). CONCLUSION: Preoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.
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BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for hepatocellular carcinoma (HCC) after liver resection (LR). This study aims to investigate the actual long-term survival and its associated prognostic factors after LR for HCC patients with MVI. METHODS: This study was conducted on HCC patients with MVI who underwent LR from January 2009 to December 2012 at five major hospitals in China. The patients were divided into the 'long-term survivor group' and the 'short-term survivor group'. The clinicopathologic characteristics, perioperative data and survival outcomes were compared between these two groups. Univariate and multivariate regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1517 patients with an actual 5-year survival rate of 33.3%. Multivariate regression analysis revealed that HBV DNA > 104 IU/mL, alanine aminotransferase > 44 U/L, alpha-fetoprotein > 400 ng/ml, anatomical hepatectomy, varices, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor number, satellite nodules, tumor encapsulation, wide resection margin and adjuvant transarterial chemoembolization (TACE) were independent prognostic factors associated with actual long-term survival. CONCLUSIONS: One-third of HCC patients with MVI reached the long-term survival milestone of 5 years after resection. Anatomical hepatectomy, controlling intraoperative blood loss, a wide resection margin, and postoperative adjuvant TACE should be considered for patients to achieve better long-term survival outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Hepatectomía , Humanos , Neoplasias Hepáticas/terapia , Invasividad Neoplásica , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) commonly occurs in patients with splenomegaly. This study aimed to investigate the impact of splenomegaly with or without splenectomy on long-term survival of HCC patients with portal vein tumor thrombus (PVTT) treated with liver resection (LR). METHODS: HCC patients with PVTT who underwent LR from 2005 to 2012 from 6 hospitals were retrospectively studied. The long-term overall survival (OS) and recurrence-free survival (RFS) were compared between patients with or without splenomegaly, and between patients who did or did not undergo splenectomy for splenomegaly. Propensity score matching (PSM) analysis was performed to match patients in a 1:1 ratio. RESULTS: Of 716 HCC patients with PVTT who underwent LR, 140 patients had splenomegaly (SM group) and 576 patients had no splenomegaly (non-SM group). The SM group was further subdivided into 49 patients who underwent splenectomy (SPT group), and 91 patients who did not received splenectomy (non-SPT group). PSM matched 140 patients in the SM group, and 49 patients in the SPT group. Splenomegaly was an independent risk factor of poor RFS and OS. The OS and RFS rates were significantly better for patients in the non-SM group than the SM group (OS: P<0.001; RFS: P<0.001), and for patients in the SPT group than the non-SPT group (OS: P<0.001; RFS: P<0.001). CONCLUSIONS: Patients who had splenomegaly had significantly worse survival in HCC patients with PVTT. Splenectomy for splenomegaly significantly improved long-term survival in these patients.
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BACKGROUND: The activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored. METHODS: Monocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed. RESULTS: TAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions. CONCLUSIONS: Our data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.
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Metionina Adenosiltransferasa/metabolismo , Metionina/metabolismo , Monocitos/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Neoplasias Gástricas/patología , Regulación hacia Arriba , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Polaridad Celular , Reprogramación Celular , Regulación Neoplásica de la Expresión Génica , Histonas/metabolismo , Humanos , Metilación , Ratones , Trasplante de Neoplasias , Regiones Promotoras Genéticas , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Macrófagos Asociados a Tumores/metabolismoRESUMEN
Nonalcoholic steatohepatitis (NASH) is a highly prevalent metabolic disorder. Currently, there are no effective pharmacotherapeutic options for preventing and treating NASH. Portulaca oleracea L. (POL) is an edible herb that has been used for preventing and treating some metabolic disorders in China, but the bioactive constituents in POL and the related mechanisms for treating NASH are still unclear. Here, a comprehensive research strategy was used to identify the core genes and the key constituents in POL for treating NASH, via integrating bioinformatics analysis and experimental pharmacology both in vitro and in vivo. The phenotypes and mechanisms of POL were carefully investigated by performing a set of in vivo and in vitro experiments. Bioinformatics analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target and myricetin (Myr) was the key constituent in POL for treating NASH. In NASH mice model induced by methionine choline deficiency diet, POL significantly alleviated hepatic steatosis and liver injury. In free fatty acids-induced hepatocytes, POL and Myr significantly down-regulated the expression of PTGS2, decreased the number of lipid droplets, and regulated the mRNA expression of lipid synthesis and homeostasis genes, including FASN, CPT1a, SERBP1c, ACC1, and SCD1. In lipopolysaccharide-induced macrophages, POL and Myr significantly reduced the expression of PTGS2 and blocked the secretion of inflammatory mediators TNF-α, IL-6, and IL-1ß. Further investigations demonstrate that Myr acts as both suppressor and inhibitor of PTGS2. Collectively, POL and its major component Myr can ameliorate NASH via down-regulating and inhibiting PTGS2, suggesting that POL and Myr can be developed as novel medicines for treating NASH.
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BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Células Neoplásicas Circulantes/patología , Vena Porta/patología , Trombosis , Supervivientes de Cáncer/estadística & datos numéricos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , China/epidemiología , Femenino , Hepatectomía/efectos adversos , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Efectos Adversos a Largo Plazo/epidemiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Trombosis/etiología , Trombosis/cirugíaRESUMEN
INTRODUCTION: Colorectal liver metastasis is a challenge in the treatment of colorectal cancer and an important factor affecting the prognosis of patients. Currently, microwave ablation has gradually been applied for the treatment of liver cancers as a type of thermal ablation. However, there are no large-scale studies on the effectiveness of microwave ablation for colorectal liver metastases. AIM: To investigate the efficacy of microwave ablation and liver resection for liver metastases from colorectal cancer, and to compare the prognosis between patients treated with microwave ablation and those in the SEER (Surveillance, Epidemiology, and End Results, National Cancer Institute) database. MATERIAL AND METHODS: We retrospectively analyzed the clinical data of 24 patients with colorectal liver metastasis who underwent radical colorectal cancer resection and liver microwave ablation (the MWA group) and 12 patients who received radical colorectal cancer resection and liver resection (the LR group). The complete ablation rate and complications after microwave ablation were observed. Survival analysis was performed for cases treated with liver resection and cases from the SEER database. RESULTS: A total of 53 tumors were ablated in the 24 patients who underwent radical colorectal cancer resection and liver microwave ablation; 52 tumors achieved complete ablation after the first ablation (98.1%). No serious complications occurred in the MWA group, and long-term survival was not significantly different between the MWA and other groups. CONCLUSIONS: Microwave ablation for colorectal liver metastases avoids extensive liver resection while ensuring therapeutic efficacy; the operation is safe, feasible, and reproducible.
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BACKGROUND: To improve the early diagnosis of hepatocellular carcinoma (HCC), more effective diagnostic biomarkers are needed. A combination of biomarkers is reported to distinguish individuals with early-stage HCC from at-risk individuals. METHODS: Participants in this study were recruited from six hospitals in China. Literature review was used to choose 19 candidate proteins, a case-control study in the discovery stage was used to identify five proteins (P5) that constituted a diagnostic model. In the training and validation stages, the effectiveness of P5 for detecting early-stage HCC was tested (cross-sectional study). Finally, a nested case-control study independent of the other stages was set up to evaluate the P5 in the preclinical diagnosis of HCC. FINDINGS: Between February 2013 and June 2017, a total of 1396 participants were recruited. A panel of 5 proteins (P5: OPN, GDF15, NSE, TRAP5 and OPG) showed high diagnostic accuracy when differentiating the early-stage HCC from the at-risk group, with AUCs of 0·892, 0·907 and 0·852 for the training stage, validation cohort 1 and cohort 2 data sets, respectively. In the prediction set, the sensitivity of P5 for diagnosing preclinical HCC increased with time, starting from 12 months before to the time of definitive clinical diagnosis (range, 46·15% to 86·67%). INTERPRETATION: The P5 panel has the potential to screen populations at high risk of developing HCC and can enable the early diagnosis of HCC. FUNDING: Research supported by grants from eight funds. All sources of funding were declared at the end of the text.
Asunto(s)
Biomarcadores de Tumor , Proteínas Sanguíneas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/epidemiología , Detección Precoz del Cáncer , Femenino , Virus de la Hepatitis B , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/virología , Humanos , Biopsia Líquida , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/epidemiología , Imagen por Resonancia Magnética , Masculino , Estadificación de Neoplasias , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration. METHODS: The differential expression of complements was explored via the Tumor Immune Estimation Resource (TIMER) site and the Oncomine database. To investigate whether these differentially expressed complements have correlation with the prognosis of gastric cancer (GC) and colon cancer, their impact on survival was assessed using the PrognoScan database and Kaplan-Meier plotter. The correlations between complements and tumor immune-infiltrating levels and immune gene markers were statistically explored in TIMER based on Spearman's correlation coefficients and p-values. RESULTS: In two colon cancer cohorts, an increased expression level of DAF (CD55) has statistically significant correlation with poor disease-free survival (DFS). High C3, CR4, and C5aR1 expression levels were significantly related with poor prognosis in GC patients. In addition, C3, CR4, and C5aR1 expression was positively related to the tumor purity and infiltration levels of multiple immune cells in stomach adenocarcinoma (STAD). Moreover, the expression levels of C3, CR4, and C5aR1 were also strongly correlated with various immune marker sets, such as those of tumor-associated macrophages (TAMs), M1 and M2 macrophages, T cell exhaustion, Tregs, and DCs, in STAD. Additionally, CD55 has positive correlation with few immune cell infiltration levels in colon adenocarcinoma (COAD), but its correlation with immune marker sets was not statistically significant. CONCLUSION: These findings confirm the relationship between various complements and tumor prognosis and immune infiltration in colon cancer and GC. CD55 may serve as an indicator on the survival prognosis of patients with colon cancer. Furthermore, as biomarkers for poor prognosis in GC, complements C3, CR4, and C5aR1 may provide potential biological targets for GC immunotherapy.