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BACKGROUND: Immunotherapy or apatinib alone has been used as third-line adjuvant therapy for advanced or metastatic gastric/gastroesophageal junction (G/GEJ) tumors, but the efficacy of combining them with each other for the treatment of patients with advanced or metastatic G/GEJ is unknown; therefore, we further evaluated the efficacy and safety of immunotherapy combined with apatinib in patients with advanced or metastatic G/GEJ. METHODS: The main search was conducted on published databases: Embase, Cochrane library, PubMed.The search was conducted from the establishment of the database to December 2023.Clinical trials with patients with advanced or metastatic G/GEJ and immunotherapy combined with apatinib as the study variable were collected. Review Manager 5.4 software as well as stata 15.0 software were used for meta-analysis. RESULTS: A total of 651 patients from 19 articles were included in this meta-analysis. In the included studies, immunotherapy combined with apatinib had a complete response (CR) of 0.03 (95% CI: 0.00 -0.06), partial response (PR) of 0.34 (95% CI: 0.19-0.49), stable disease (SD) of 0.43 (95% CI: 0.32-0.55), objective response rate (ORR) was 0.36 (95% CI: 0.23-0.48), disease control rate (DCR) was 0.80 (95% CI: 0.74-0.86), and median progression-free survival (PFS) was 4.29 (95% CI: 4.05-4.52), median Overall survival (OS) was 8.79 (95% CI: 7.92-9.66), and the incidence of grade ≥ 3 TRAEs was 0.34 (95% CI: 0:19-0.49). PR, ORR, DCR, median PFS and median OS were significantly higher in the immunotherapy and apatinib combination chemotherapy group (IAC) than in the immunotherapy combination apatinib group (IA). And the difference was not significant in the incidence of SD and grade ≥ 3 TRAEs. CONCLUSION: This meta-analysis shows that immunotherapy combined with apatinib is safe and effective in the treatment of advanced or metastatic G/GEJ, where IAC can be a recommended adjuvant treatment option for patients with advanced or metastatic G/GEJ. However, more large multicenter randomized studies are urgently needed to reveal the long-term outcomes of immunotherapy combined with apatinib treatment.
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Neoplasias Esofágicas , Unión Esofagogástrica , Inmunoterapia , Piridinas , Neoplasias Gástricas , Humanos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/terapia , Inmunoterapia/métodos , Unión Esofagogástrica/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: The causal associations of circulating lipids with Barrett's Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. METHODS: We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 - 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. RESULTS: None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). CONCLUSION: This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.
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Esófago de Barrett , Neoplasias Esofágicas , Humanos , Esófago de Barrett/genética , Análisis de la Aleatorización Mendeliana , Reproducibilidad de los Resultados , Neoplasias Esofágicas/genética , Triglicéridos , Lípidos , Estudio de Asociación del Genoma CompletoRESUMEN
Background: Neoadjuvant therapy for resectable gastric cancer/gastroesophageal junction tumors is progressing slowly. Although immunotherapy for advanced gastric cancer/gastroesophageal junction tumors has made great progress, the efficacy and safety of neoadjuvant immunotherapy for locally resectable gastric cancer/gastroesophageal junction tumors have not been clearly demonstrated. Here, we conducted a systematic review and meta-analysis to assess the efficacy and safety of neoadjuvant immunotherapy and advance the current research. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy for resectable gastric cancer/gastroesophageal junction tumors published up until October 15, 2023 were retrieved from PubMed, Embase, the Cochrane Library, and other major databases. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated for heterogeneity and subgroup analysis. Results: A total of 1074 patients from 33 studies were included. The effectiveness of neoadjuvant immunotherapy was mainly evaluated using pathological complete remission (PCR), major pathological remission (MPR), and tumor regression grade (TRG). Among the included patients, 1015 underwent surgical treatment and 847 achieved R0 resection. Of the patients treated with neoadjuvant immunotherapy, 24% (95% CI: 19%-28%) achieved PCR and 49% (95% CI: 38%-61%) achieved MPR. Safety was assessed by a surgical resection rate of 0.89 (95% CI: 85%-93%), incidence of ≥ 3 treatment-related adverse events (TRAEs) of 28% (95% CI: 17%-40%), and incidence of ≥ 3 immune-related adverse events (irAEs) of 19% (95% CI: 11%-27%). Conclusion: Neoadjuvant immunotherapy, especially neoadjuvant dual-immunotherapy combinations, is effective and safe for resectable gastric/gastroesophageal junction tumors in the short term. Nevertheless, further multicenter randomized trials are required to demonstrate which combination model is more beneficial. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=358752, identifier CRD42022358752.
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Neoplasias Esofágicas , Unión Esofagogástrica , Inmunoterapia , Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Terapia Neoadyuvante/métodos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/inmunología , Unión Esofagogástrica/patología , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/inmunología , Resultado del TratamientoRESUMEN
OBJECTIVE: The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma. METHODS: Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed. RESULTS: A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = - 0.09, 95% CI: -0.20 to - 0.03, I2 = 20%, p = 0.13), body mass index (BMI; SMD = - 0.10, 95% CI: -0.21 to - 0.01, I2 = 0%, p = 0.08), thymoma size (SMD = - 0.01, 95% CI: -0.01, I2 = 0%, p = 0.08), operative time (SMD = - 0.70, 95% CI: -1.43-0.03, I2 = 97%, p = 0.06), intraoperative bleeding (SMD = - 0.30. 95% CI: -0.66-0.06, I2 = 89%, p = 0.10), time to extubation (SMD = - 0.34, 95%CI: -0.73-0.05, I2 = 91%, p = 0.09), postoperative hospital stay (SMD = - 0.40, 95% CI: -0.93-0.12, I2 = 93%, p = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42-2.12, I2 = 57%, p = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = - 0.43, 95%CI: -0.84 to - 0.02, I2 = 88%, p = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = - 1.73, 95%CI: -2.27 to - 1.19, I2 = 93%, p < 0.00001), 3 (SMD = - 1.88, 95%CI: -2.84 to - 0.81, I2 = 97%, p = 0.0005), and 7 (SMD = - 1.18, 95%CI: -2.28 to - 0.08, I2 = 97%, p = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant (p > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant (p < 0.05) in the MSVATS group compared with the IVATS group. CONCLUSION: The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.
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Timoma , Neoplasias del Timo , Humanos , Timoma/patología , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/métodos , Neoplasias del Timo/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Dolor Postoperatorio/etiologíaRESUMEN
[This corrects the article DOI: 10.1016/j.isci.2023.106103.].
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CDCP1 is a transmembrane protein that is involved in a variety of important biological processes and upregulated in a variety of human solid malignancies; however, its spatial distribution and variation at the molecular level remain unclear. To solve this problem, we first analyzed its expression level and prognostic implications in lung cancer. Then, we used super-resolution microscopy to reveal the spatial organization of CDCP1 at different levels, and found that cancer cells generated more and larger CDCP1 clusters than normal cells. Furthermore, we found that CDCP1 can be integrated into larger and denser clusters as functional domains upon activation. Our findings elucidated the significant differences of CDCP1 clustering characteristics between cancer and normal cells, and revealed the relationship between its distribution and function, which will contribute to a comprehensive understanding of its oncogenic mechanism, and will be of great help for the development of CDCP1-targeted drugs for lung cancer.
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CUB domain-containing protein 1 (CDCP1), as an emerging transmembrane protein, is overexpressed in a variety of malignant tumors including respiratory tumors, digestive system cancers, hematological malignancies and urogenital cancers. Several cancer-related proteins have been reported to interact with CDCP1. It acts as a crucial hub in multiple classical signaling pathways of tumorigenesis and progression. Its overexpression and activation are also associated with prognosis and drug resistance. Due to its important roles in malignant tumors, CDCP1 is expected to be a promising therapeutic target for treatment and a new biomarker for diagnosis. In this article, we review the roles of CDCP1 in diagnosis and management of malignant tumors, and also its regulation in several essential tumor-related pathways.
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Antígenos de Neoplasias , Neoplasias , Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular , Línea Celular Tumoral , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Transducción de SeñalRESUMEN
As a transmembrane protein, CD47 plays an important role in mediating cell proliferation, migration, phagocytosis, apoptosis, immune homeostasis, inhibition of NO signal transduction and other related reactions. Upon the interaction of innate immune checkpoint CD47-SIRPα occurrence, they send a "don't eat me" signal to the macrophages. This signal ultimately helps tumors achieve immune escape by inhibiting macrophage contraction to prevent tumor cells from phagocytosis. Therefore, the importance of CD47-SIRPα immune checkpoint inhibitors in tumor immunotherapy has attracted more attention in recent years. Based on the cognitive improvement of the effect with CD47 in tumor microenvironment and tumor characteristics, the pace of tumor treatment strategies for CD47-SIRPα immune checkpoint inhibitors has gradually accelerated. In this review, we introduced the high expression of CD47 in cancer cells to avoid phagocytosis by immune cells and the importance of CD47 in the structure of cancer microenvironment and the maintenance of cancer cell characteristics. Given the role of the innate immune system in tumorigenesis and development, an improved understanding of the anti-tumor process of innate immune checkpoint inhibitors can lay the foundation for more effective combinations with other anti-tumor treatment strategies.
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Antígenos de Diferenciación/inmunología , Antígeno CD47/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunidad Innata/inmunología , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Receptores Inmunológicos/inmunología , Animales , Humanos , Inmunoterapia/métodos , Macrófagos , Neoplasias/inmunología , Fagocitosis , Escape del Tumor , Microambiente TumoralRESUMEN
The transmembrane glycoprotein Trop2 plays important roles in various types of human cancers, especially lung cancer. Although it has been found to form clusters on cancer cell membranes, the factors that affect its clustering are not yet fully understood. Here, using direct stochastic optical reconstruction microscopy (dSTORM), we found that Trop2 generated more, larger, and denser clusters on apical cell membranes than on basal membranes and that the differences might be related to the different membrane structures. Moreover, dual-color dSTORM imaging revealed significant colocalization of Trop2 and lipid rafts, and methyl-ß-cyclodextrin disruption dramatically impaired the formation of Trop2 clusters, indicating a key role of lipid rafts in Trop2 clustering. Additionally, depolymerization of the actin cytoskeleton decreased Trop2 cluster numbers and areas, revealing that actin can stabilize the clusters. More importantly, stimulation of Trop2 in cancer cells hardly changed the cluster morphology, suggesting that Trop2 is activated and forms clusters in cancer cells. Altogether, our work links the spatial organization of Trop2 to different membrane structures and Trop activation and uncovers the essential roles of lipid rafts and actin in Trop2 cluster maintenance.
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Transmembrane glycoprotein Trop2 is related to many epithelial carcinomas. It not only plays roles in promoting fetal lung growth but also participates in tumor genesis, malignant transformation, and tumor dissemination. However, the detailed distribution of Trop2 at the molecular level remains unknown. Herein, we used direct stochastic optical reconstruction microscopy to reveal the spatial organization of Trop2 on the membranes of cultured and primary lung cancer cells and normal cells. All types of cancer cells presented more localizations of Trop2 than normal cells. By SR-Teseller cluster analysis, we found that Trop2 existed in the form of clusters on all the membranes; however, cancer cells generated more and larger clusters consisting of more molecules than normal cells. Our findings shed light on the heterogeneous distribution of membrane Trop2 and highlighted the significant differences of its clustering characteristics between lung cancer cells and normal cells, which laid the basis for further studying the mechanism and functions of Trop2 clustering in lung cancer.
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Antígenos de Neoplasias/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Moléculas de Adhesión Celular/metabolismo , Membrana Celular/metabolismo , Neoplasias Pulmonares/patología , Imagen Óptica , Línea Celular Tumoral , HumanosRESUMEN
Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.
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Platinum nanoparticles (PtNPs) were uniformly grown on the surface of gold nanorods (AuNRs) by a laser irradiation procedure. Transmission electron microscopy confirmed that the PtNPs are uniformly grown on the surface of the AuNRs. The formation of PtNPs on the AuNRs leads to a red-shift of the absorption maximum from 734 nm to 766 nm. In addition, the efficiency of surface enhanced Raman scattering (SERS) is increased, but the photothermal conversion efficiency is decreased compared to pure AuNRs. The result indicates that electron transfer occurs between gold and platinum. The peroxidase mimicking effect of PtNPs, AuNRs and Au/Pt NRs by catalyzing the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB; a quinone) in the presence of H2O2. The catalytic activity of Au/Pt NRs is higher than that of sole AuNRs or PtNPs by factors of 4.2 and 2.1, respectively. Thus, Au/Pt NRs have been used for the detection of peroxide and the limit of detection is 0.04 µM. This work provides an approach to integrate the peroxidase mimicking effect with SERS enhancement for potential application in detection. Graphical abstract A schematic diagram for the laser-induced growth of Au/Pt NRs and the colorimetric determination of hydrogen peroxide concentration with their peroxidase mimicking properties. The limit of detection is 0.04 µM based on the use of Au/Pt NRs as a catalyst.
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BACKGROUND: The correlation between O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and esophageal cancer remains controversial. This study was conducted to evaluate the clinical effect of MGMT promoter methylation on esophageal carcinoma patients. METHODS: A literature search was conducted in the PubMed, EMBASE, EBSCO, and Cochrane Library databases. The overall OR and corresponding 95% CI were calculated using the random-effects model. RESULTS: Finally, 17 eligible studies were identified in this meta-analysis; these studies included a total of 1,368 patients with esophageal carcinoma and 1,489 with nonmalignant controls. MGMT promoter methylation was significantly higher in esophageal carcinoma tissue samples than in nonmalignant tissue samples (OR 3.64, p < 0.001). Promoter methylation of the MGMT gene was not associated with gender, cigarette smoking, drinking behavior, or tumor differentiation, but MGMT promoter methylation was correlated with age (≥60 vs. <60 years: OR 1.64, p = 0.028), lymph node status (positive status vs. negative status: OR 2.39, p = 0.024), and clinical stage (stages 3-4 vs. 1-2: OR 10.59, p < 0.001). CONCLUSIONS: Our findings suggest that MGMT promoter methylation may be correlated with esophageal cancer carcinogenesis and could be associated with age, lymph node status, and clinical stage.
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Metilación de ADN/genética , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/genética , O(6)-Metilguanina-ADN Metiltransferasa/genética , Regiones Promotoras Genéticas , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Casos y Controles , Neoplasias Esofágicas/patología , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , Sesgo de Publicación , Factores de Riesgo , Fumar/efectos adversosRESUMEN
BACKGROUND: Epilepsy is the second most common disease caused by multiple factors and characterized by an excessive discharge of certain neurons in the nervous system. Cerebrovascular disease, including stroke, is viewed as the most common cause of epilepsy in the elderly population, accounting for 30%-50% of the newly diagnosed cases of epilepsy cases in this age group. METHODS: Data were collected from Web of Science, Medline, Pubmed, Scopus, through searching of these keywords: "Stroke" and "epilepsy". RESULTS: Depending on the underlying cerebrovascular disease, 3%-30% of patients after stroke may develop post-stroke epilepsy (PSE), which has a negative effect on stroke prognosis and the quality of life. CONCLUSION: In this review, we summarized new aspects emerging from research into PSE, including definition, epidemiology, risk factors, mechanism, accessory examination and treatment strategies for post-stroke epilepsy, which will enrich our knowledge of this disorder.