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1.
Surg Endosc ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914889

RESUMEN

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

2.
J Immunother Cancer ; 12(5)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782541

RESUMEN

BACKGROUND: Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive. RESULTS: The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379-3 p to promote M2 macrophage polarization. CONCLUSION: circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor-macrophage interaction potentially affecting CRC metastatic nodule formation.


Asunto(s)
Neoplasias Colorrectales , Exosomas , Interleucina-10 , Macrófagos , ARN Circular , Factor de Transcripción STAT3 , Animales , Femenino , Humanos , Masculino , Ratones , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Exosomas/metabolismo , Interleucina-10/metabolismo , Activación de Macrófagos , Macrófagos/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Macrófagos Asociados a Tumores/metabolismo
3.
Cell Death Dis ; 15(4): 238, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561367

RESUMEN

Macrophages, as pivotal cells within the tumour microenvironment, significantly influence the impact of and reactions to treatments for solid tumours. The rapid evolution of bioengineering technology has revealed the vast potential of engineered macrophages in immunotherapy, disease diagnosis, and tissue engineering. Given this landscape, the goal of harnessing and innovating macrophages as a novel strategy for solid tumour immunotherapy cannot be overstated. The diverse strategies for engineered macrophages in the realm of cancer immunotherapy, encompassing macrophage drug delivery systems, chimeric antigen receptor macrophage therapy, and synergistic treatment approaches involving bacterial outer membrane vesicles and macrophages, are meticulously examined in this review. These methodologies are designed to enhance the therapeutic efficacy of macrophages against solid tumours, particularly those that are drug-resistant and metastatic. Collectively, these immunotherapies are poised to supplement and refine current solid tumour treatment paradigms, thus heralding a new frontier in the fight against malignant tumours.


Asunto(s)
Inmunoterapia , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/patología , Macrófagos/patología , Inmunoterapia Adoptiva , Sistemas de Liberación de Medicamentos , Microambiente Tumoral
4.
J Neurooncol ; 167(1): 63-74, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38427133

RESUMEN

BACKGROUND: Glioma is a type of malignant cancer that affect the central nervous system. New predictive biomarkers have been investigated in recent years, but the clinical prognosis for glioma remains poor. The function of CPLX2 in glioma and the probable molecular mechanism of tumor suppression were the focus of this investigation. METHODS: The glioma transcriptome profile was downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases for analysis of CPLX2 expression in glioma. RT-qPCR was performed to detect the expression of CPLX2 in 68 glioma subjects who have been followed up. Kaplan-Meier survival analyses were conducted to assess the effect of CPLX2 on the prognosis of glioma patients. The knockdown and overexpressed cell lines of CPLX2 were constructed to investigate the impact of CPLX2 on glioma. The cell growth, colony formation, and tumor formation in xenograft were performed. RESULTS: The expression of CPLX2 was downregulated in glioma and was negatively correlated with the grade of glioma. The higher expression of CPLX2 predicted a longer survival, as indicated by the analysis of Kaplan-Meier survival curves. Overexpressed CPLX2 impaired tumorigenesis in glioma progression both in vivo and in vitro. Knocking down CPLX2 promoted the proliferation of glioma cells. The analysis of GSEA and co-expression analysis revealed that CPLX2 may affect the malignancy of glioma by regulating the hypoxia and inflammation pathways. CONCLUSIONS: Our data indicated that CPLX2 functions as a tumor suppressor and could be used as a potential prognostic marker in glioma.


Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular , Neoplasias Encefálicas , Glioma , Proteínas Supresoras de Tumor , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/metabolismo , Glioma/patología , Estimación de Kaplan-Meier , Pronóstico , Transcriptoma , Proteínas del Tejido Nervioso/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
5.
Antib Ther ; 7(1): 77-87, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38371956

RESUMEN

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by dysregulated immune responses. The key mediators of AD pathogenesis are T helper 2 (TH2) cells and TH2 cytokines. Targeting interleukin 4 (IL4), IL13 or IL31 has become a pivotal focus in both research and clinical treatments for AD. However, the need remains pressing for the development of a more effective and safer therapy, as the current approaches often yield low response rates and adverse effects. In response to this challenge, we have engineered a immunoglobulin G-single-chain fragment variable (scFv) format bispecific antibody (Ab) designed to concurrently target IL4R and IL31R. Our innovative design involved sequence optimization of VL-VH and the introduction of disulfide bond (VH44-VL100) within the IL31Rα Ab scFv region to stabilize the scFv structure. Our bispecific Ab efficiently inhibited the IL4/IL13/IL31 signaling pathways in vitro and reduced serum immunoglobulin E and IL31 levels in vivo. Consequently, this intervention led to improved inflammation profiles and notable amelioration of AD symptoms. This research highlighted a novel approach to AD therapy by employing bispecific Ab targeting IL4Rα and IL31Rα with potent efficacy.

6.
J Ethnopharmacol ; 326: 117923, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38367929

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS) is a traditional prescription for the treatment of liver depression and qi stagnation, and pharmacological studies have shown that XYS has great potential to reverse depression. However, anti-depression targets and the mechanism of XYS are still not entirely clear. AIM OF THE STUDY: The present study aims to explore and verify the anti-depression mechanism of XYS. MATERIALS AND METHODS: The antidepressant effect of XYS was assessed in rats with depression induced by chronic unpredictable mild stimulation (CUMS). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in different brain regions were measured using ELISA. The expression of organic cation transporters (Octs) were detected by western blot and immunohistochemical techniques. Then, Decynium-22 (D22), an Octs inhibitor, was injected into the prefrontal cortex (PFC) to verify the correlation between Octs and depression-like behavior. Then, the effects of XYS on the behavior, neurotransmitter concentration, and Octs expression in D22-induced rats were examined. Finally, primary astrocytes were used to verify the mechanism of XYS exerting anti-depressant activity by regulating Octs. RESULTS: The result showed that XYS had a significant positive impact on the behavior of depression rats induced by CUMS. XYS also improved the secretion of 5-HT, DA, and NE in the PFC, as well as the promotion of Oct1, Oct2, and Oct3 expression in the PFC. These results suggest that XYS has the potential to alleviate depression by enhancing the secretion of neurotransmitters. This may be related to XYS regulation of Oct's expression. When the expression of Octs was inhibited in the PFC, rats exhibited behavior similar to depression, and XYS was able to reverse this behavior, indicating that Octs play a significant role in the development of depression and XYS may exert its antidepressant effects through the regulation of Octs. Furthermore, the study also found that dopamine uptake decreased after inhibiting the expression of Octs, and XYS-containing serum could reverse the downregulation of Oct1 and Oct3 and promote intracellular dopamine homeostasis in the astrocytes. Overall, XYS may exert antidepressant effects by promoting dopamine uptake to improve neurotransmitter transport by regulating the protein expression of Oct1 and Oct3 in astrocytes. CONCLUSIONS: The antidepressant effect of XYS may be attributed to its ability to regulate the expression of Oct1 and Oct3 in astrocytes of the PFC, thereby promoting neurotransmitter transport.


Asunto(s)
Astrocitos , Depresión , Medicamentos Herbarios Chinos , Ratas , Animales , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/metabolismo , Dopamina , Serotonina , Conducta Animal , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Corteza Prefrontal , Neurotransmisores
7.
J Transl Med ; 22(1): 30, 2024 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184566

RESUMEN

BACKGROUND: Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. METHODS: Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo. RESULTS: We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway. CONCLUSIONS: This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Animales , Humanos , Ratones , Neoplasias Colorrectales/genética , Neoplasias Hepáticas/genética , FN-kappa B , Linfocitos T , Microambiente Tumoral , Factor de Necrosis Tumoral alfa
8.
iScience ; 27(2): 108779, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38292420

RESUMEN

Immune escape is identified as one of the reasons for the poor prognosis of colorectal cancer (CRC) patients. Circular RNAs are considered to promote tumor progression by mediating tumor immune escape. We discovered that higher expression of circYAP1 was associated with a worse prognosis of CRC patients. Functional experiments in vitro and in vivo showed that circYAP1 upregulation inhibited the cytotoxicity of CD8+ T cells by upregulating programmed death ligand-1 (PD-L1). Mechanistically, we found that circYAP1 directly binds to the YAP1 protein to prevent its phosphorylation, enhancing proportion of YAP1 protein in the nucleus, and that YAP1 interacts with TCF4 to target the PD-L1 promoter and initiate PD-L1 transcription in CRC cells. Taken together, circYAP1 promotes CRC immune escape and tumor progression by activating the YAP1/TCF4-PD-L1 axis and may provide a new strategy for combination immunotherapy of CRC patients.

9.
Cancer Gene Ther ; 31(2): 259-272, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38052858

RESUMEN

This study was designed to investigate the role and mechanism of cancer-associated fibroblasts (CAFs)-derived exosomes (CAFs-exo) in metastatic and chemoresistant colorectal cancer (CRC). First, CAFs and normal fibroblasts (NFs) were isolated from CRC tissues and histologically normal adjacent tissues. Then, CAFs-exo and NFs-exo were separated with the help of ultracentrifugation. Next, the morphology, diameter and marker expression of exos were evaluated by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot, respectively. Besides, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of LINC00355, miR-34b-5p, and CRKL in clinical tissue samples, CRC cells, fibroblasts and exos; MTT assay and cell colony formation assay to assess the chemoresistance and colony formation ability of CRC cells, respectively. Subsequently, the targeting relationship among LINC00355, miR-34b-5p, and CRKL (a target gene of miR-34b-5p) was verified by Luciferase reporter assay; and the binding relationship between LINC00355 and miR-34b-5p was assessed by a pull-down assay. Finally, the expression of epithelial-mesenchymal transition (EMT)-related proteins, and CRKL in cells or exos were detected using western blot. After a series of treatments, CAFs and NFs, CAFs-exo and NFs-exo were successfully isolated and identified. It could be observed that CAFs-exo promoted EMT, colony formation and multidrug resistance in CRC cells by secreting LINC00355. Further studies demonstrated that CAFs-exo-secreted LINC00355 increased the expression of CRKL via inhibiting the expression of miR-34b-5p, thereby enhancing chemoresistance and promoting EMT progression in CRC cells. Collectively, CAFs-exo-derived LINC00355 promotes EMT and chemoresistance in CRC by regulating the miR-34b-5p/CRKL axis.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Colorrectales , Exosomas , MicroARNs , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/genética , Transición Epitelial-Mesenquimal/genética , Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo
10.
Mol Cancer ; 22(1): 203, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38087360

RESUMEN

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.


Asunto(s)
Exosomas , Vesículas Extracelulares , Neoplasias , Humanos , Neoplasias/patología , Vesículas Extracelulares/genética , Exosomas/patología , Comunicación Celular , Inmunoterapia , Microambiente Tumoral
11.
Mol Cancer ; 22(1): 198, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-38053093

RESUMEN

Tumor angiogenesis plays vital roles in the growth and metastasis of cancer. RNA methylation is one of the most common modifications and is widely observed in eukaryotes and prokaryotes. Accumulating studies have revealed that RNA methylation affects the occurrence and development of various tumors. In recent years, RNA methylation has been shown to play an important role in regulating tumor angiogenesis. In this review, we mainly elucidate the mechanisms and functions of RNA methylation on angiogenesis and progression in several cancers. We then shed light on the role of RNA methylation-associated factors and pathways in tumor angiogenesis. Finally, we describe the role of RNA methylation as potential biomarker and novel therapeutic target.


Asunto(s)
Neoplasias , Humanos , Metilación , Neoplasias/genética , Neoplasias/patología , Neovascularización Patológica/genética , ARN/genética
13.
Front Oncol ; 11: 743703, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34778061

RESUMEN

Colorectal cancer (CRC), a seriously threat that endangers public health, has a striking tendency to relapse and metastasize. Redox-related signaling pathways have recently been extensively studied in cancers. However, the study and potential role of redox in CRC remain unelucidated. We developed and validated a risk model for prognosis and recurrence prediction in CRC patients via identifying gene signatures driven by redox-related signaling pathways. The redox-driven prognostic signature (RDPS) was demonstrated to be an independent risk factor for patient survival (including OS and RFS) in four public cohorts and one clinical in-house cohort. Additionally, there was an intimate association between the risk score and tumor immune infiltration, with higher risk score accompanied with less immune cell infiltration. In this study, we used redox-related factors as an entry point, which may provide a broader perspective for prognosis prediction in CRC and have the potential to provide more promising evidence for immunotherapy.

14.
Front Pharmacol ; 12: 717529, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34483925

RESUMEN

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.

15.
Vaccine ; 39(30): 4135-4143, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34116877

RESUMEN

Hand-foot-and-mouth disease (HFMD) is an infectious disease of infants and young children frequently caused by the enterovirus A species, mainly enterovirus 71 (EV71) and coxsackievirus A16 (CA16). In this study, we prepared the EV71 virus-like particle (EV71-VLP) and its chimeras using recombinant baculovirus (Bac-P1-3CD) co-expressing EV71 P1 (under polyhedrin promoter) and 3CD (under CMV-IE promoter) proteins in Sf9 cells. EV71-VLP chimera ChiEV71(1E)-VLP or ChiEV71(4E)-VLP displayed single CA16 PEP71 epitope in VP1 or four conserved CA16 neutralizing epitopes (PEP71 in VP1, aa136-150 in VP2, aa176-190 in VP3 and aa48-62 in VP4) by substitution of the corresponding regions of EV71 structure proteins, respectively. In mice, EV71-VLP and its chimeras elicited similar EV71-specific IgG and neutralizing antibody (NAb) titers compared to inactivated EV71. Expectedly, vaccination of ChiEV71(1E)-VLP or ChiEV71(4E)-VLP resulted in significantly increased CA16-specific IgG and NAb production and improved cross-protection against CA16 infection compared to EV71-VLP. Interestingly, the VLPs induced potent cellular immune responses and significantly decreased Th2 type (IL-4 and IL-10) cytokines secretion in the splenocytes of immunized mice compared to inactivated EV71 or inactivated CA16. Neonatal mice born to dams immunized with the chimeric VLPs or neonatal mice passively transferred with sera of immunized mice were completely protected from lethal EV71 challenge and partially protected from lethal CA16 infection. Our study provides a novel bivalent or multivalent vaccine strategy to prevent EV71 and related-enterovirus infections.


Asunto(s)
Enterovirus Humano A , Enterovirus , Enfermedad de Boca, Mano y Pie , Vacunas Virales , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Quimera , Protección Cruzada , Enterovirus Humano A/genética , Epítopos/genética , Enfermedad de Boca, Mano y Pie/prevención & control , Ratones , Vacunas Virales/genética
16.
Sci Rep ; 11(1): 1571, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33452440

RESUMEN

To explore the predictive performance of machine learning on the recurrence of patients with gastric cancer after the operation. The available data is divided into two parts. In particular, the first part is used as a training set (such as 80% of the original data), and the second part is used as a test set (the remaining 20% of the data). And we use fivefold cross-validation. The weight of recurrence factors shows the top four factors are BMI, Operation time, WGT and age in order. In training group:among the 5 machine learning models, the accuracy of gbm was 0.891, followed by gbm algorithm was 0.876; The AUC values of the five machine learning algorithms are from high to low as forest (0.962), gbm (0.922), GradientBoosting (0.898), DecisionTree (0.790) and Logistic (0.748). And the precision of the forest is the highest 0.957, followed by the GradientBoosting algorithm (0.878). At the same time, in the test group is as follows: the highest accuracy of Logistic was 0.801, followed by forest algorithm and gbm; the AUC values of the five algorithms are forest (0.795), GradientBoosting (0.774), DecisionTree (0.773), Logistic (0.771) and gbm (0.771), from high to low. Among the five machine learning algorithms, the highest precision rate of Logistic is 1.000, followed by the gbm (0.487). Machine learning can predict the recurrence of gastric cancer patients after an operation. Besides, the first four factors affecting postoperative recurrence of gastric cancer were BMI, Operation time, WGT and age.


Asunto(s)
Predicción/métodos , Recurrencia Local de Neoplasia/fisiopatología , Neoplasias Gástricas/fisiopatología , Anciano , Algoritmos , China , Femenino , Humanos , Modelos Logísticos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Neoplasias Gástricas/cirugía
17.
Front Cell Dev Biol ; 9: 798319, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35174160

RESUMEN

The protein kinase C (PKC) family has been described with its role in some cancers, either as a promoter or suppressor. PKC signaling also regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha (PPARalpha). However, the role of different PKC enzymes in tumor immunity remains poorly defined. This study aims to investigate the correlation between PKC genes and tumor immunity, in addition to studying the probability of their use as predictive biomarkers for tumor immunity and immunotherapeutic response. The ssGSEA and the ESTIMATE methods were used to assess 28 tumor-infiltrating lymphocytes (TILs) and the immune component of each cancer, then correlated with PKC levels. Prediction of PKC levels-dependent immunotherapeutic response was based on human leukocytic antigen (HLA) gene enrichment scores and programmed cell death 1 ligand (PD-L1) expression. Univariate and multivariate Cox analysis was performed to evaluate the prognostic role of PKC genes in cancers. Methylation level and CNAs could drive the expression levels of some PKC members, especially PRKCI, whose CNGs are predicted to elevate their level in many cancer types. The most crucial finding in this study was that PKC isoenzymes are robust biomarkers for the tumor immune status, PRKCB, PRKCH, and PRKCQ as stimulators, while PRKCI and PRKCZ as inhibitors in most cancers. Also, PKC family gene levels can be used as predictors for the response to immunotherapies, especially HLAs dependent and PD-L1 blockade-dependent ones. In addition to its prognostic function, all PKC family enzymes are promising tumor immunity biomarkers and can help select suitable immune therapy in different cancers.

18.
World J Clin Cases ; 8(14): 3021-3030, 2020 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-32775383

RESUMEN

BACKGROUND: Colorectal cancer is one of the most common cancers globally. In China, its prevalence ranks fourth and fifth among females and males, respectively. Presently, treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery, radiotherapy, chemotherapy, and targeted therapy. With deepening theoretical and molecular research on colorectal cancer, randomized controlled trials (RCTs) on colorectal cancer have made significant progress. However, many RCTs have shortfalls. AIM: To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018. To provide suggestions for conducting Chinese RCTs of colorectal cancer. METHODS: PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1, 2008, and January 1, 2018. The bibliometric method was used for statistical analysis of the publication years, countries/regions, authors, institutions, source journals, quoted times, key words, and authors. RESULTS: Colorectal cancer RCTs showed an upward trend between 2008 to 2018; the top 10 research institutions in the included literature were from the United States, the United Kingdom, and other countries with a high incidence of colorectal cancer. Most of the related research journals are sponsored by European and American countries. The 15 most cited studies involved international multicenter clinical research, having few participants from Chinese research institutions. Network visualization using key words showed that RCTs on colorectal cancer focus on screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life, and prognosis. The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries. CONCLUSION: High-quality RCTs are increasingly favored by leading international journals. However, there is still a large gap in clinical research between China and leading countries. Researchers should implement standardized and accurate clinical trials, strengthen international multicenter cooperation, and emphasize quality control.

19.
Clin Transl Med ; 10(2): e49, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32536040

RESUMEN

BACKGROUND: Estrogen receptor (ER) is essential in reproductive development and is also the primary driver of breast cancers. Deregulation of ER may also be involved in tumorigenesis of other organs. To understand the role of ER in different tumor types, pan-cancer analysis of estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) in various tumors and association with patients' survival were conducted using The Cancer Genome Atlas (TCGA) data. RESULTS: Gene methylation level was evaluated by the mean methylation level of CpG sites in the promoter region. The significant different DNA methylation between tumor and healthy tissues was shown in 10 tumor types for ESR1 and eight tumor types for ESR2. The methylation pattern was also varied across different TCGA tumors. The pan-cancer analysis showed significantly different mRNA expression of ESR1 in nine tumor types and ESR2 in four tumor types. Survival analysis showed that the effects of ERs expression on survival are diverse in different tumors. The expression of ERs was associated with tumor molecular subtypes and various clinical characteristics. ER correlated genes were mainly enriched in cancer and immune-related pathways. CONCLUSIONS: Our pan-cancer analysis data indicated that ERs might be significantly associated with carcinogenesis and progression of some tumors, which may be potential therapeutic targets and prognosis biomarkers.

20.
Int J Surg ; 72: 102-108, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31362128

RESUMEN

BACKGROUND: Recently, the incidence of colorectal cancer has increased each year. Natural orifice specimen extraction surgery (NOSES) removes the specimen from a natural cavity of the human body (anal or vaginal) and completes reconstruction of the digestive tract. There are only a few trocar scars in the abdomen after surgery. Transvaginal specimen extraction for right-sided colon cancer is one of the classic NOSES surgeries. As NOSES is accepted by increasing numbers of colorectal surgeons, NOSES technology is becoming increasingly widely used in China and abroad. Studies have confirmed the feasibility and safety of NOSES. Therefore, it is necessary to conduct further clinical studies to evaluate the short-term efficacy of the NOSES procedure. OBJECTIVE: To investigate the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer (NOSES). METHODS: We conducted a retrospective analysis of 90 cases of laparoscopic right colon cancer radical surgery performed continuously in the anorectal surgery of our Hospital from June 2015 to December 2018. Thirty-two patients underwent complete laparoscopic anastomosis and transvaginal specimen removal (NOSES group), and 58 patients underwent conventional abdominal wall removal specimen surgery (LAP group). The general data of the patients were matched by the propensity score matching (PSM) method 1:1. Thirty-one pairs of cases were successfully matched, and the intraoperative and postoperative data were analysed. RESULTS: After PSM, the baseline data were balanced between the two groups. A total of 62 patients in the two groups were successfully operated without conversion. There were no significant differences in intraoperative blood loss, lymph node dissection, sputum tumour cell positive rate, bacterial culture positive rate, postoperative follow-up and postoperative pelvic floor function evaluation (P > 0.05). Neither tumour cells nor bacteria were detected in the rinse solution at the start of the operation. Compared with the LAP group, the incidence of postoperative complications was lower in the NOSES group (6.4% vs. 29.0%, P = 0.006), and the gastrointestinal function recovery time was shorter (2.58 ±â€¯0.92 vs. 3.42 ±â€¯0.92, P = 0.001), postoperative hospital stay was shorter (6.68 ±â€¯1.47 vs. 9.58 ±â€¯2.22, P < 0.001), postoperative pain score was lower (postoperative day 1: 2.35 ±â€¯1.52 vs. 4.87 ±â€¯1.50; postoperative day 3: 1.81 ±â€¯1.11 vs. 4.00 ±â€¯1.18; postoperative day 5: 1.45 ±â€¯1.00 vs. 2.97 ±â€¯1.17; P < 0.001), additional analgesic drug use rate was lower (12.9% vs. 61.3%, P < 0.001), and patients were more satisfied with the appearance of the abdominal wall after surgery (100% vs. 23.6%, P < 0.001). CONCLUSION: This study used PSM to remove confounding factors and retrospectively analysed the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer radical resection. The results showed that the laparoscopic right colon cancer radical resection was satisfactory, ensuring sterility. At the same time, there is a clear advantage in reducing postoperative pain, shortening postoperative hospital stays, reducing the incidence of postoperative complications, and improving the appearance of the abdominal wall.


Asunto(s)
Neoplasias del Colon/cirugía , Puntaje de Propensión , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Vagina
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