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1.
Front Oncol ; 14: 1370111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567163

RESUMO

Periampullary cancer is a malignant tumor occurring around the ampullary region of the liver and pancreas, encompassing a variety of tissue types and sharing numerous biological characteristics, including interactions with the nervous system. The nervous system plays a crucial role in regulating organ development, maintaining physiological equilibrium, and ensuring life process plasticity, a role that is equally pivotal in oncology. Investigations into nerve-tumor interactions have unveiled their key part in controlling cancer progression, inhibiting anti-tumor immune responses, facilitating invasion and metastasis, and triggering neuropathic pain. Despite many mechanisms by which nerve fibers contribute to cancer advancement still being incompletely understood, the growing emphasis on the significance of nerves within the tumor microenvironment in recent years has set the stage for the development of groundbreaking therapies. This includes combining current neuroactive medications with established therapeutic protocols. This review centers on the mechanisms of Periampullary cancer's interactions with nerves, the influence of various types of nerve innervation on cancer evolution, and outlines the horizons for ongoing and forthcoming research.

2.
Front Biosci (Landmark Ed) ; 29(2): 80, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38420812

RESUMO

The incidence and mortality from malignant tumors continue to rise each year. Consequently, early diagnosis and intervention are vital for improving patient' prognosis and survival. The traditional pathological tissue biopsy is currently considered the gold standard for cancer diagnosis. However, it suffers from several limitations including invasiveness, sometimes not repeatable or unsuitable, and the inability to capture the dynamic nature of tumors in terms of space and time. Consequently, these limit the application of tissue biopsies for the diagnosis of early-stage tumors and have redirected the research focus towards liquid biopsies. Blood-based liquid biopsies have thus emerged as a promising option for non-invasive assessment of tumor-specific biomarkers. These minimally invasive, easily accessible, and reproducible tests offer several advantages, such as being mostly complication-free and efficient at monitoring tumor progression and tracing drug resistance. Liquid biopsies show great potential for cancer prediction, diagnosis, and prognostic assessment. Circulating tumor-educated platelets (TEPs) possess the unique ability to absorb nucleic acids from the bloodstream and to modify transcripts derived from megakaryocytes in response to external signals. In addition, circulating free RNA (cfRNA) constitutes a significant portion of the biomolecules present in the bloodstream. This paper aims to provide a comprehensive overview of the current research status regarding TEP RNA and cfRNA in liquid biopsies from various tumor types. Our analysis includes cancers of the lung, liver, pancreas, breast, nasopharynx, ovary and colon, as well as multiple myeloma and sarcoma. By synthesizing this information, we intend to establish a solid theoretical foundation for exploring potential applications of circulating RNA as a reliable biomarker for tumor diagnosis and monitoring.


Assuntos
Ácidos Nucleicos Livres , Neoplasias , Células Neoplásicas Circulantes , Feminino , Humanos , Ácidos Nucleicos Livres/genética , Biópsia Líquida , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , RNA/genética , RNA Neoplásico , Biomarcadores Tumorais/genética , Células Neoplásicas Circulantes/patologia
3.
Front Biosci (Landmark Ed) ; 28(11): 297, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38062829

RESUMO

Toll-like receptor 3 (TLR3) is a prominent member of the Toll-like receptor (TLR) family and has the ability to recognize and bind intracellular double-stranded RNA (dsRNA). Once triggered by a viral infection or other pathological condition, TLR3 activates immune cells and induces the production of interferons and other immune response molecules. Additionally, TLR3 is considered an important immune modulator, as it can regulate cell apoptosis and promote anticancer immunity. The investigation and application of TLR3 agonists in digestive system tumors have attracted widespread attention and are regarded as a promising cancer treatment strategy with potential clinical applications. TLR3 expression levels are generally elevated in most digestive system tumors, and higher TLR3 expression is associated with a better prognosis. Therefore, TLR3 has emerged as a novel therapeutic target for digestive system tumors. It has been used in combination with chemotherapy, radiotherapy, and targeted therapy and demonstrated excellent efficacy and tolerability. This has provided new ideas and hopes for the treatment of digestive system tumors. This review discusses the mechanisms of TLR3 and its frontier research in digestive system tumors.


Assuntos
Neoplasias do Sistema Digestório , Neoplasias Gastrointestinais , Humanos , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/metabolismo , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , RNA de Cadeia Dupla , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/agonistas , Receptor 3 Toll-Like/metabolismo , Receptores Toll-Like
4.
World J Gastrointest Surg ; 15(11): 2423-2429, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38111773

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is closely related to obesity, and weight loss can significantly improve the metabolic, endocrine and reproductive functions of obese individuals with PCOS. However, the efficacy of laparoscopic sleeve gastrectomy (LSG) for obesity with PCOS are unclear. AIM: The purpose of the study was to investigate the effect of LSG on related variables in obese patients with PCOS. METHODS: A retrospective analysis was performed on 32 obese patients with PCOS who received LSG treatment at the Third Hospital of Shanxi Medical University from 2013 to 2020. The changes in anthropometric indices, insulin, testosterone, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), menstrual cycle and LH/FSH ratio before and 1 mo, 3 mo, 6 mo and 12 mo after the operation were statistically analyzed. RESULTS: At 1 mo, 3 mo, 6 mo and 12 mo after surgery, the anthropometric indices, such as body weight and body mass index, of all patients were lower than those before the operation. The percentage excess weight loss (EWL%) at 1 mo, 3 mo, 6 mo and 1 year of follow-up were 25, 40, 46 and 65, respectively. The PCOS-related indices, such as insulin, testosterone, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and menstrual cycle, were improved to varying degrees. During the 1-year follow-up, the average serum testosterone decreased from preoperative 0.72 ng/mL to 0.43 ng/mL (P < 0.05), average fasting insulin level (9.0 mIU/mL, preoperative 34.2 mil, LH level, 4.4 mIU/mL, preoperative 6.1 mIU/mL). The level of FSH (3.8 U/L, 4.8 U/p0.05) and the ratio of LH/FSH (0.7, 1.3/p0.05) were more relieved than those before surgery. During the postoperative follow-up, it was found that the menstrual cycle of 27 patients (nasty 27) returned to normal, and 6 patients (18%) who intended to become pregnant became pregnant within 1 year after surgery. CONCLUSION: The weight loss effect of LSG is obvious and affirmative, and the endocrine index of obese patients with PCOS is also improved to some extent, although the mechanism is not clear. Laparoscopic sleeve gastrectomy is expected to become a backup choice for patients with polycystic ovaries in the future.

5.
Open Life Sci ; 18(1): 20220748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941781

RESUMO

There is growing evidence that higher body mass index (BMI) is associated with lower survival in breast cancer patients. The aim of this study was to investigate whether there is an association between body mass index (BMI) at breast cancer diagnosis and breast cancer prognosis and whether this association is dependent on menopausal status and tumor subtype in a less developed population in northern China. We collected 1,225 patients with primary invasive cancer in stage I-IIIC for retrospective analysis from October 2010 to December 2020. We used Kaplan-Meier and Cox regression analyses and estimated the relationship between baseline BMI and breast cancer-specific survival (BCSS). Next, we further evaluated whether the effect of BMI on breast cancer prognosis differed by menopausal status and tumor subtype. We found that death rate and prognosis were worse for patients with BMI ≥ 24, more than four positive lymph nodes, and triple negative status. Interestingly, BMI played a different prognostic role depending on tumor subtype and menopausal status. For premenopausal women, patients with BMI ≥ 24 had significantly lower BCSS compared to those with BMI < 24 in human epidermal growth factor receptor 2 (HER2) overexpression (HR: 4.305, p = 0.004) and triple negative subtypes (HR: 1.775, p = 0.048). By contrast, there was no association between BMI ≥ 24 and higher death regardless of tumor subtype in post-menopausal patients (p > 0.05). BMI influences breast cancer outcome depending on tumor subtype and menopause. BMI ≥ 24 might be a risk factor for BCSS, particularly in premenopausal women with HER2 overexpression or triple negative subtype. In contrast, BMI ≥ 24 was not associated with higher death regardless of tumor subtype in post-menopausal patients.

6.
J Hepatocell Carcinoma ; 10: 1767-1784, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841370

RESUMO

Purpose: Cyclin-dependent kinase regulatory subunit 2 (CKS2) has an important function in regulating cancer progression and cell cycle. This research aims to ascertain how CKS2 plays its part through multi-omics analyses, to reveal its relationship with the immune microenvironment in hepatocellular carcinoma (HCC). Material and Methods: Multiple databases were used to determine the transcriptional data of CKS2, epigenetic changes, and effects thereof upon the prognosis of HCC patients. The biological functions of CKS2 in HCC were expounded by functional enrichment analysis. TIMER, GSEA, TIP, and online single-cell sequencing databases were adopted for revealing correlations of CKS2 expression with infiltration of immune cells, immunomodulators, immunity cycle, and immune markers in the immune microenvironment of HCC. In addition, qRT-PCR and Western blot were used to validate gene expression in tissues from HCC patients. Results: Open database analysis confirmed that CKS2 is highly expressed in HCC and that it is related to poor prognosis in HCC patients. Aberrant methylation levels of the two methylation sites of CKS2 in HCC contributed to its high expression and were correlated significantly with survival. The CKS2 expression was positively correlated with most immunomodulators and infiltration levels for B and CD8+T cells, dendritic cells, and macrophages, especially exhausted CD8+T cells. Besides, the CKS2 expression was also found to have significant correlations with immunity cycle steps and diverse immune markers in HCC. The high CKS2 expression was confirmed in HCC at both mRNA and protein levels, showing a significant increase compared to normal tissue. Conclusion: CKS2 is a potential prognostic biomarker of HCC and can promote the progression of HCC via its influences on the immune environment. Additionally, a positive correlation between CKS2 and immune markers was observed, highlighting its potential as an immunotherapeutic target.

7.
iScience ; 26(6): 106862, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37275516

RESUMO

Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/ß-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to ß-catenin, leading to disassociation of ß-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/ß-catenin/YAP1 axis in HCC stemness and progression.

8.
Neural Netw ; 162: 502-515, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36972650

RESUMO

Multi-view stereo reconstruction aims to construct 3D scenes from multiple 2D images. In recent years, learning-based multi-view stereo methods have achieved significant results in depth estimation for multi-view stereo reconstruction. However, the current popular multi-stage processing method cannot solve the low-efficiency problem satisfactorily owing to the use of 3D convolution and still involves significant amounts of calculation. Therefore, to further balance the efficiency and generalization performance, this study proposed a multi-scale iterative probability estimation with refinement, which is a highly efficient method for multi-view stereo reconstruction. It comprises three main modules: 1) a high-precision probability estimator, dilated-LSTM that encodes the pixel probability distribution of depth in the hidden state, 2) an efficient interactive multi-scale update module that fully integrates multi-scale information and improves parallelism by interacting information between adjacent scales, and 3) a Pi-error Refinement module that converts the depth error between views into a grayscale error map and refines the edges of objects in the depth map. Simultaneously, we introduced a large amount of high-frequency information to ensure the accuracy of the refined edges. Among the most efficient methods (e.g., runtime and memory), the proposed method achieved the best generalization on the Tanks & Temples benchmarks. Additionally, the performance of the Miper-MVS was highly competitive in DTU benchmark. Our code is available at https://github.com/zhz120/Miper-MVS.


Assuntos
Benchmarking , Generalização Psicológica , Aprendizagem , Probabilidade
9.
Front Genet ; 13: 996890, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303541

RESUMO

Tumors are a class of diseases characterized by altered genetic information and uncontrolled growth. Sequencing technology provide researchers with a better way to explore specific tumor pathogenesis. In recent years, single-cell sequencing technology has shone in tumor research, especially in the study of liver cancer, revealing phenomena that were unexplored by previous studies. Single-cell sequencing (SCS) is a technique for sequencing the cellular genome, transcriptome, epigenome, proteomics, or metabolomics after dissociation of tissues into single cells. Compared with traditional bulk sequencing, single-cell sequencing can dissect human tumors at single-cell resolution, finely delineate different cell types, and reveal the heterogeneity of tumor cells. In view of the diverse pathological types and complex pathogenesis of hepatocellular carcinoma (HCC), the study of the heterogeneity among tumor cells can help improve its clinical diagnosis, treatment and prognostic judgment. On this basis, SCS has revolutionized our understanding of tumor heterogeneity, tumor immune microenvironment, and clonal evolution of tumor cells. This review summarizes the basic process and development of single-cell sequencing technology and its increasing role in the field of hepatocellular carcinoma.

10.
Oxid Med Cell Longev ; 2022: 4277254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299605

RESUMO

DNA topoisomerases (TOPs) are dysregulated in various types of cancer. However, how TOP II-alpha (TOP2A) contributes to hepatocellular carcinoma (HCC) progression remains elusive. Cohort analysis revealed that the increased expression of TOP2A was associated with poor clinical outcomes and TOP2A was significantly upregulated in HCC tissues and cell lines. In vitro, TOP2A expression level is related to cell invasion and migration, which may be due to the alteration of epithelial-mesenchymal transition by the TOP2A. Moreover, we used verteporfin (a Hippo inhibitor) to test how the Hippo pathway promotes the effect of TOP2A on the HCC phenotype and found that TOP2A induces tumor progression through the Hippo pathway. Finally, miR-22-5p inhibited tumor progression by sponging TOP2A.


Assuntos
Carcinoma Hepatocelular , DNA Topoisomerases Tipo II , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo/genética , Via de Sinalização Hippo/fisiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Verteporfina
11.
Oxid Med Cell Longev ; 2022: 1592786, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193079

RESUMO

Obese patients can significantly reduce weight and have a positive impact on obesity-related diseases. However, the risk of infection complications in obese people is higher than that in normal people, especially the surgical site infection. This research investigates the effect of antibiotics on weight change of obese patients after laparoscopic sleeve gastrectomy (LSG). A retrospective analysis was performed on 131 morbidly obese patients or obese patients with complications who received LSG treatment in the Third Hospital of Shanxi Medical University from 2013 to 2020. Patients were separated into the antibiotic group (59 cases) and the normal group (72 cases) according to whether antibiotics were used after surgery. The differences of postoperative weight-related indexes, inflammation-related indexes, and short-term complications were compared between the two groups. At 12-month follow-up, the % excess weight loss (%EWL) in the antibiotic group was statistically abated than that in the normal group (92.99 ± 28.60, P < 0.01). In addition, the percentage of total weight loss (%total weight loss (%TWL)) was abated in the antibiotic group than in the normal group, but it was not significant (P > 0.05). White blood cell count and neutrophil count in the antibiotic group were statistically raised than those in the in normal group (P < 0.05), but neutrophil/lymphocyte ratio (NLR) showed no significant difference. Comparison of short-term postoperative complications between the two groups showed that the number of abdominal wall wound infection, body temperature > 38°C, and abdominal pain > 3 days in the antibiotic group were abated, but they were not statistically significant (P > 0.05). Short-term antibiotic exposure after sleeve gastrectomy had an adverse effect on postoperative weight loss, with no significant improvement in short-term complications.


Assuntos
Laparoscopia , Obesidade Mórbida , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Índice de Massa Corporal , Gastrectomia , Humanos , Laparoscopia/efeitos adversos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso
12.
Turk J Gastroenterol ; 33(12): 1050-1057, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36098361

RESUMO

BACKGROUND: Pancreatic duct stones obstruct the pancreatic ducts and aggravate clinical symptoms of chronic pancreatitis. Only isolated case reports have shown that some drugs may be useful in dissolving pancreatic duct stones. Endothelium corneum gigeriae galli is a Chinese medicine widely used to cure multifarious lithiasis and maldigestion. This study aimed to evaluate the efficacy of endothelium corneum gigeriae galli oral therapy in the dissolution of stones and evaluate the improvement of clinical symptoms in patients with pancreatic duct stones. METHODS: Sixty-eight patients with pancreatic duct stones were randomly divided into the endothelium corneum gigeriae galli and control groups. Endothelium corneum gigeriae galli was given orally to the endothelium corneum gigeriae galli group, and the placebo was given to the control group. Both groups were reviewed by computed tomography and magnetic resonance imaging; abdominal pain, exocrine and endocrine pancreatic function, and the nutritional status of patients were measured after the study. RESULTS: The dissolution rate of the endothelium corneum gigeriae galli group was significantly higher than that of the control group (P = .002). The abdominal pain of the endothelium corneum gigeriae galli group was relieved more significantly compared to that of the control group (P < .001). The exocrine and endocrine pancreatic function of the endothelium corneum gigeriae galli group improved more significantly than that of the control group (P < .001). The nutritional status of the endothelium corneum gigeriae galli group was significantly higher than that of the control group (P = .003). CONCLUSION: Overall, oral endothelium corneum gigeriae galli treatment could dissolve pancreatic duct stones, relieve abdominal pain, improve exocrine and endocrine pancreatic functions, and control the deterioration of nutritional status. Endothelium corneum gigeriae galli treatment should be useful in pancreatic duct stones therapy.


Assuntos
Litotripsia , Pancreatopatias , Pancreatite Crônica , Humanos , Estudos Prospectivos , Pancreatopatias/tratamento farmacológico , Ductos Pancreáticos , Pancreatite Crônica/terapia , Dor Abdominal , Colangiopancreatografia Retrógrada Endoscópica
13.
Front Immunol ; 13: 921900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865544

RESUMO

Hypersplenism (HS) is a concomitant symptom of liver or blood disease. Not only does the treatment of HS face challenges, but the transcriptome of individual cells is also unknown. Here, the transcriptional profiles of 43,037 cells from four HS tissues and one control tissue were generated by the single-cell RNA sequencing and nine major cell types, including T-cells, B-cells, NK cells, hematopoietic stem cells, neutrophil cells, mast cells, endothelial cells, erythrocytes, and dendritic cells were identified. Strikingly, the main features were the lack of CCL5+ B-cells in HS and the presence of SESN1+ B cells in HS with hepatocellular carcinoma (HS-HCC). In cell-cell interaction analysis, CD74-COPA and CD94-HLA-E in HS were found to be up-regulated. We further explored HS-specifically enriched genes (such as FKBP5, ADAR, and RPS4Y1) and found that FKBP5 was highly expressed in HCC-HS, leading to immunosuppression. Taken together, this research provides new insights into the genetic characteristics of HS via comprehensive single-cell transcriptome analysis.


Assuntos
Carcinoma Hepatocelular , Hiperesplenismo , Doenças do Sistema Imunitário , Neoplasias Hepáticas , Complexo Antígeno-Anticorpo , Carcinoma Hepatocelular/patologia , Células Endoteliais/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Análise de Sequência de RNA
14.
Medicine (Baltimore) ; 101(5): e28620, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35119006

RESUMO

ABSTRACT: We retrospectively reviewed the medical records of patients with pathologically confirmed gastric cancer/adenocarcinoma who underwent curative surgical resection follow-up within 3 years at Shanxi cancer hospital between 2002 and 2020. The clinicopathologic parameters explored included gender, age at surgery, vascular invasion, neural invasion, Tumor infiltration depth (T stage), N stage, TNM stage, chemotherapy, Lauren classification, maximum diameter of tumor, type of gastrectomy, tumor location and survival data.With a median follow-up of 29 months (range 0-36 months), the ratio of patients with recurrence was 26.80% (n = 226) and the death rate of patients was 45.31% (n = 382) in this period. According to the results of univariate analysis, gender (P = .014), age at surgery (P = .010), vascular invasion (P = .000), neural invasion (P = .000), T stage (P = .000), N stage (P = .000), TNM stage (P = .000), chemotherapy cycle (P = .000), lauren classification (P = .000), maximum diameter of tumor (P = .000), type of gastrectomy (P = .000) were independent risk factors of recurrence of follow-up within 3 years. From the multivariate analysis by logistic regression showed that TNM Stage (P = .002), chemotherapy cycle (P = .000) were risk factors of recurrence of follow-up within 3 years. Univariate analysis of survival by Kaplan-Meier showed that gender (P = .038), vascular invasion (P = .000), neural invasion (P = .000), maximum diameter of tumor (P = .000), Lauren classification (P = .000), T stage (P = .000), N stage (P = .000), TNM Stage (P = .000) and type of gastrectomy (P = .000) were key factors linked to overall survival of follow-up within 3 years. The results of the multivariate analysis by Cox regression were clearly presented that T Stage (P = .000), TNM stage (P = .001), maximum diameter of tumor (P = .001) were key factors of overall survival of follow-up within 3 years.TNM Stage, chemotherapy cycle were closely related to recurrence and of follow-up within 3 years. More than 9 cycles of chemotherapy was able to reduce the probability of recurrence. T Stage, TNM stage, maximum diameter of tumor were independent factors associated with overall survival of gastric cancer of follow-up within 3 years. For maximum diameter of tumor, the probability of death of more than 6 cm was 1.317 times less than 6 cm within 3 years of follow-up.


Assuntos
Adenocarcinoma , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Seguimentos , Gastrectomia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
15.
Gene ; 821: 146250, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35151825

RESUMO

Mounting evidences have indicated that RNA N6-methyladenosine (m6A) modification played important roles in tumor formation and growth. However, it is rarely reported that m6A modifications are involved in the immune regulation and tumor microenvironment (TME) formation. In this study, we aimed to investigate the correlation between m6A modifications and TME regulation of colon adenocarcinoma (COAD) by bioinformatic analysis. NMF algorithm was applied to carry out consensus molecular subtype analysis on 36 selected m6A regulators regarding methylation modification, to identify m6A modification patterns and characteristics of m6A related genes in colon adenocarcinoma (COAD). Further, the relative infiltration levels of different immune cell subsets were quantified by ssGSEA and CIBERSORT algorithms, and a m6Sig scoring scheme was constructed to predict the prognosis and evaluate the response to immunotherapy in the patients with COAD. Among 579 COAD samples, we identified three different m6A modification patterns which were related to different biological pathways and clinical outcomes. Then, a scoring scheme termed "m6Sig score" was developed based on m6A-related characteristic genes, and was utilized to score patients with COAD into groups. We found that COAD patients with lower m6Sig scores exhibited prolonged survival and potentiated immune infiltration, which were associated with higher tumor mutation load, lower PD-L1 expression, and higher mutation rates of SMG (such as TTN and KRAS). Moreover, analysis regarding evaluation of immune response revealed that the patients with lower m6Sig scores had higher Immunophenoscore. Collectively, our study provided in depth insight into the interactions between m6A modification and regulation of TME. In addition, the quantitative evaluation of m6A modification patterns in our results may have implications in further immunotherapy for individual COAD patients.


Assuntos
Adenosina/análogos & derivados , Neoplasias do Colo/genética , Biologia Computacional/métodos , Metilação de DNA , Redes Reguladoras de Genes , Adenosina/metabolismo , Algoritmos , Antígeno B7-H1/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Conectina/genética , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sobrevida , Microambiente Tumoral
16.
Pathol Res Pract ; 232: 153808, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35217267

RESUMO

BACKGROUND: Prefoldin complex subunits (PFDNs) and prefoldin-like complex subunits (PFDLNs) collaborate in protein folding, modulate endoplasmic reticulum stress. The association between PFDN/PFDLN and the immune microenvironment of HCC remains unclear. We investigated the biological significance of PFDNs and PFDLNs in HCC using bioinformatics. METHODS: The relationship between PFDNs/PFDLNs and HCC was analysed using TCGA, and Human Protein Atlas. The protein-protein interaction (PPI) network was performed through String and Cytoscape. In addition, mutations in PFDNs and PFDLNs were analysed using cBioPortal. Clinical correlation analysis, survival analysis was conducted by using UALCAN and Kaplan-Meier analysis. The protein-protein interaction (PPI) network was performed through String and Cytoscape. The GO and KEGG enrichment analyses were also carried out. CCK-8 and Flow cytometry analysis were used to detect the proliferation and apoptosis of PFDN1 and UXT knockdown HCC cells. Immune infiltrates analyses was were conducted using the TIMER and TISIDB to determine whether PFDNs/PFDLNs are predictive biomarkers of immune cell infiltration. RESULTS: We observed that PFDNs and PFDLNs were significantly overexpressed in HCC tissues compared to normal liver tissues. This abnormal expression was associated with worse clinicopathological features and negatively affected patient survival. PFDNs and PFDLNs have varying degrees of mutations in HCC, which may be related to their abnormal expression. In addition, up-regulated PFDN1 and UXT were found to promote HCC proliferation and inhibit apoptosis in vitro. Finally, the expression of certain PFDNs and PFDLNs in the tumour microenvironment was positively correlated with the level of tumour-infiltrating immune cells and significantly enhanced the infiltration of immune cells in the microenvironment. CONCLUSIONS: PFDNs and PFDLNs are valuable predictive biomarkers for immune infiltration in HCC and may assist in tumour immunotherapy research and prognosis prediction in the future.


Assuntos
Carcinoma Hepatocelular , Imunoterapia , Neoplasias Hepáticas , Chaperonas Moleculares , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Proteínas de Ciclo Celular , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Chaperonas Moleculares/genética , Prognóstico , Microambiente Tumoral
17.
J Microbiol Biotechnol ; 31(10): 1331-1342, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34373436

RESUMO

In this study, we evaluated the mechanism of long non-coding RNA MIR22 host gene (LncRNA MIR22HG) in osteosarcoma cells. Forty-eight paired osteosarcoma and adjacent tissues samples were collected and the bioinformatic analyses were performed. Target genes and potential binding sites of MIR22HG, microRNA (miR)-629-5p and tet methylcytosine dioxygenase 3 (TET3) were predicted by Starbase and TargetScan V7.2 and confirmed by dual-luciferase reporter assay. Cell Counting Kit-8, colony formation and flow cytometry assays were utilized to determine the viability, proliferation and apoptosis of transfected osteosarcoma cells. Pearson's analysis was introduced for the correlation analysis between MIR22HG and miR-629-5p in osteosarcoma tissue. Relative expressions of MIR22HG, miR-629-5p and TET3 were measured by quantitative real-time polymerase chain reaction or Western blot. MiR-629-5p could competitively bind with and was negatively correlated with MIR22HG, the latter of which was evidenced by the high expression of miR-629-5p and low expression of MIR22HG in osteosarcoma tissues. Overexpressed MIR22HG repressed the viability and proliferation but enhanced apoptosis of osteosarcoma cells, which was reversed by miR-629-5p upregulation. TET3 was the target gene of miR-629-5p, and the promotive effects of upregulated miR-629-5p on the viability and proliferation as well as its repressive effect on apoptosis were abrogated via overexpressed TET3. To sum up, overexpressed MIR22HG inhibits the viability and proliferation of osteosarcoma cells, which was achieved via regulation of the miR-629-5p/TET3 axis.


Assuntos
Neoplasias Ósseas/genética , Dioxigenases/genética , MicroRNAs/genética , Osteossarcoma/genética , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos
18.
Oncol Lett ; 22(2): 626, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34267818

RESUMO

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 in vitro. Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells in vitro. In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3'-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells.

19.
BMC Surg ; 21(1): 284, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090388

RESUMO

BACKGROUND: Full-thickness rectal prolapse (FTRP) frequently occurs in elderly women, and more than 100 surgical procedures have been proposed to restore FTRP. The Gant-Miwa-Thiersch (GMT) procedure is the most used treatment in China. However, the recurrence rate of FTRP post-GMT, which is as high as 23.8%, is concerning. We described a new modified GMT combined with internal and external rectal sclerosant injection (nmGMTSI) procedure to address this problem. METHODS: The nmGMTSI was performed under spinal anesthesia in 34 frail, elderly female patients with FTRP. The surgical results of FTRP were assessed. Fecal incontinence and constipation were evaluated using the Wexner score, and anal canal rest pressure (ACRP), maximum anal systolic pressure (MASP), anorectal sensation thresholds (AST), and maximum rectal tolerance (MRT) using anorectal manometry preoperatively and postoperatively. The causes of recurrence and complications were analyzed. RESULTS: All patients were cured according to the clinical cure standard. The perioperative Wexner fecal incontinence score (WFIS) was 10.3 ± 3.31, which became 3.7 ± 2.43 (P < 0.0001) postoperatively. The perioperative ACRP was 2.0 ± 0.56 kPa, which became 8.5 ± 2.25 kPa (P < 0.0001) postoperatively. The perioperative MASP was 4.5 ± 1.16 kPa, which became 18.6 ± 2.50 kPa (P < 0.0001) postoperatively. However, no significant difference was observed between the preoperative and postoperative Wexner constipation scores (WCS) (17.3 ± 2.25 vs. 15.4 ± 2.89, P = 0.1047). The perioperative and postoperative AST were 38.1 ± 5.34 mL and 23.5 ± 3.61 mL, respectively (P = 0.0002). The maximum rectal tolerance (MRT) was 157.1 ± 16.73 mL, which became 121.2 ± 12.45 mL postoperatively (P = 0.0009). The patients developed no serious postoperative complications. The total relapse rate after nmGMTSI was 2.9% in the median two years follow-up period. The most common cause of relapse after nmGMTSI was the removal of infected threads used in the Thiersch procedure. CONCLUSION: The benefits of nmGMTSI include low rates of recurrence, complications, and mortality, cost-effectiveness, wide adaptation, minimal invasiveness, and technical simplicity. Hence, it should be considered the first option for the treatment of FTRP in frail elderly women.


Assuntos
Prolapso Retal , Soluções Esclerosantes , Idoso , China , Feminino , Humanos , Prolapso Retal/cirurgia , Reto/cirurgia , Escleroterapia
20.
Technol Cancer Res Treat ; 20: 15330338211027912, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190015

RESUMO

BACKGROUND: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). METHODS: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. RESULTS: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. CONCLUSION: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.


Assuntos
Carcinoma de Células em Anel de Sinete/patologia , Nomogramas , Neoplasias Gástricas/patologia , Neoplasias Abdominais , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/terapia , Feminino , Gastrectomia , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores Raciais , Programa de SEER , Fatores Sexuais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Taxa de Sobrevida , Estados Unidos
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