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1.
BJS Open ; 7(4)2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37584435

RESUMO

BACKGROUND: Previous meta-analyses reporting significant associations between perioperative allogeneic blood transfusions and poor prognosis in gastric cancer or colorectal cancer had a high risk of confounding bias. This meta-analysis explored this issue using observational studies that applied propensity score analysis. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for manuscripts published between 2013 and 2022. Studies applying propensity score analysis were included to investigate the association between perioperative allogeneic blood transfusions and prognosis in gastric cancer or colorectal cancer after radical surgery. Pooled HRs for overall survival and disease-free survival were calculated using a fixed-effect model or random-effect model according to heterogeneity. RESULTS: Twelve retrospective cohort studies with 17 607 patients reported were included. Ten studies applied propensity score matching and two applied inverse probability of treatment weighting using propensity score. A total of 5962 patients were analysed after propensity score adjustment. After propensity score adjustment, perioperative allogeneic blood transfusions did not correlate with disease-free survival in gastric cancer (HR 1.16; 95 per cent c.i. 0.96-1.39; heterogeneity was assessed by the chi-squared test and inconsistency index (I2) = 57 per cent) or colorectal cancer (HR 1.12; 95 per cent c.i. 0.84-1.49; I2 = 54 per cent). However, after propensity score adjustment, perioperative allogeneic blood transfusions were significantly associated with worse overall survival in gastric cancer (HR 1.20; 95 per cent c.i. 1.08-1.32; I2 = 25 per cent) and colorectal cancer (HR 1.40; 95 per cent c.i. 1.06-1.85; I2 = 52 per cent). Subgroup analyses showed that perioperative allogeneic blood transfusions did not correlate with overall survival in colorectal cancer when major postoperative complications were balanced after propensity score. CONCLUSION: Perioperative allogeneic blood transfusion is not correlated with recurrence of gastric cancer and colorectal cancer. Perioperative allogeneic blood transfusions are significantly associated with worse overall survival in gastric cancer and colorectal cancer, which may be attributable to unbalanced major postoperative complications after propensity score adjustment.


Assuntos
Neoplasias Colorretais , Transplante de Células-Tronco Hematopoéticas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Transfusão de Sangue , Neoplasias Colorretais/cirurgia , Complicações Pós-Operatórias , Estudos Observacionais como Assunto
2.
Int J Oncol ; 63(1)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37264959

RESUMO

Long noncoding RNAs (lncRNAs) are a type of regulatory molecule with potential roles in the development of several different malignancies. However, the underlying mechanisms of lncRNAs in colorectal cancer (CRC) are incompletely understood. The present study investigated the molecular mechanism of LINC02038 in CRC. LINC02038 expression was decreased in CRC tissues compared to the para­cancerous tissues and LINC02038 overexpression markedly reduced the proliferation, vitality, migration and invasive ability and greatly accelerated apoptosis of colorectal cancer cells. Bioinformatics examination indicated that LINC02038 may have targeted microRNA (miR)­552­5p. RNA immunoprecipitation and luciferase reporter assays showed that LINC02038 served as a sponge for miR­552­5p, hindering target gene FAM172A of miR­552­5p degradation. Moreover, methylated RNA immunoprecipitation (MeRIP)­qualitative PCR assays revealed that YTHDF2 could identify and regulate the METTL3­mediated LINC02038 N6­methyladenosine (m6A) modification and increase its degradation, thereby promoting CRC progression via the PI3K/AKT pathway. Based on the CRC clinical specimens, it was shown that LINC02038 was negatively associated with lymphatic metastasis and distant metastasis. These results revealed that m6A/LINC02038/miR­552­5p/FAM172A may be a novel anti­tumor axis and LINC02038 may serve as a biomarker and treatment option for colorectal cancer.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Ligação Competitiva , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Colorretais/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Metiltransferases/metabolismo , Proteínas/genética
3.
Sci Rep ; 13(1): 8265, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217530

RESUMO

Gastric cancer has been one of the wide public health burdens with its high morbidity and mortality over several decades. As the unconventional modules among RNA families, circular RNAs present their blazing biological effects during gastric carcinogenesis. Though diverse hypothetical mechanisms were reported, further tests were necessitated for authentication. Herein, this study pinpointed a representative circDYRK1A which screened from vast amounts of public data sets using surprisingly novel bioinformatics approaches together with validations from the in vitro findings and then concluded that circDYRK1A tethered the biological behavior and swayed the clinicopathological features with gastric cancer patients thus providing an in-depth awareness for gastric carcinoma.


Assuntos
Carcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Regulação Neoplásica da Expressão Gênica , RNA/genética , Biologia Computacional , Carcinoma/genética
4.
J Oncol ; 2023: 7097909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816363

RESUMO

Long noncoding (lnc) RNAs regulate cancer progression. However, the importance of lncRNAs and how they are regulated in colorectal cancer (CRC) are unclear. We aim to evaluate the function of lncRNA ADAMTS9-AS2 in CRC and its fundamental mechanism. Levels of ADAMTS9-AS2, miR-27a-3p, and B-cell translocation gene 2 (BTG2) were measured by qPCR. Cell viability was analyzed by CCK-8 and colony formation. Migration and invasion were tested by transwell assay. The interactions among ADAMTS9-AS2, miR-27a-3p, BTG2, and YTHDF2 were analyzed by luciferase test, immunoblotting, RNA pull-down, or RNA immunoprecipitation (RIP). An animal model was adopted to assess ADAMTS9-AS2's function. Overexpressing ADAMTS9-AS2 inhibited cell migration, invasion, colony formation capacity, and proliferation in vitro. The direct targeting of miR-27a-3p by ADAMTS9-AS2 abrogated the latter's effect in CRC cells. BTG2 was identified a target of miR-27a-3p, and silencing BTG2 weakened miR-27a-3p's effect. Knocking down ADAMTS9-AS2 abolished sh-YTHDF2's inhibitory effect on cell proliferation and invasion. Finally, overexpressing ADAMTS9-AS2 restrained xenograft growth. M6A reader YTHDF2-mediated degradation of ADAMTS9-AS2 promotes colon carcinogenesis via miR-27a-3p/BTG2 axis.

5.
Cancers (Basel) ; 15(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36672345

RESUMO

Glioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPR/Cas9 gene-editing technology in the treatment of glioma. As an emerging gene-editing technology, CRISPR/Cas9 utilizes the expression of certain functional proteins to repair tissues or treat gene-deficient diseases and could be applied to immunotherapies through the expression of antigens, antibodies, or receptors. In addition, some research also utilized CRISPR/Cas9 to establish tumor models so as to study tumor pathogenesis and screen tumor prognostic targets. This paper mainly discusses the roles of CRISPR/Cas9 in the treatment of glioma patients, the exploration of the pathogenesis of neuroglioma, and the screening targets for clinical prognosis. This paper also raises the future research prospects of CRISPR/Cas9 in glioma, as well as the opportunities and challenges that it will face in clinical treatment in the future.

6.
Dis Markers ; 2022: 1292648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408463

RESUMO

Introduction: The global incidence of brain tumors, the most common of which is lower grade glioma (LGG), remains high. Pleckstrin homology domain-containing family A member 4 (PLEKHA4) has been reported to be related to tumor invasion and growth. However, its role and correlation with immunity in LGG remain elusive. Methods: We evaluated the expression pattern, prognostic value, biological functions, and immune effects of PLEKHA4 in LGG. We also analyzed the association between PLEKHA4 levels in different tumors, patient prognosis, and its role in tumor immunity. Depending on the type of research data, we used statistical methods such as Student's t-tests, Mann-Whitney U tests one-way ANOVA tests Kruskal-Wallis tests Pearson's or Spearman's correlation analysis Chi-square and Fisher's exact tests in this paper. Results and Conclusions. The results revealed that PLEKHA4 levels were markedly elevated in most tumors (such as LGG). High PLEKHA4 levels are associated with poor overall survival (OS), progression-free interval (PFI) rates, and disease-specific survival (DSS) in LGG patients. Cox regression analysis and nomograms showed that PLEKHA4 levels are independent prognostic factors for LGG patients. According to functional enrichment analysis, PLEKHA4 levels in LGG are associated with immune infiltration and immunotherapy. In conclusion, PLEKHA4 is a potential prognostic marker and immunotherapy target for LGG.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Domínios de Homologia à Plecstrina , Glioma/patologia , Neoplasias Encefálicas/metabolismo , Análise de Regressão
9.
Sci Rep ; 12(1): 9233, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35655081

RESUMO

Pyroptosis is a novel type of programmed cell death, initiated by inflammasome. Pyroptosis inhibits the development and metastasis of colon cancer and is associated with patients' prognosis. However, how the pyroptosis-related genes predict the survival of patients is still unclear. In the study, colon adenocarcinoma (COAD) patients were divided into two groups according to the expression of pyroptosis-related regulators through consensus clustering. DEGs between two clusters were analyzed by using COX and Lasso regression. Then, regression coefficients in Lasso were used to calculate the risk score for every patient. Patients were classified into two types: low- and high-risk group according to their risk score. The difference of immune microenvironment infiltration and clinicopathological characteristics between subgroups was performed. Moreover, the nomogram model was built on the bases of risk model and clinicopathological factors. The TCGA-COAD cohort and GEO cohort were used as training and validating set respectively. 398 COAD patients in TCGA training set were identified as two regulation patterns via unsupervised clustering method. Patients in cluster 2 showed better prognosis (P = 0.002). Through differentiated expression analysis, COX and Lasso regression, a 5-gene prognostic risk model was constructed. This risk model was significantly associated with OS (HR: 2.088, 95% CI: 1.183-3.688, P = 0.011), validated in GEO set (HR:1.344, 95%CI: 1.061-1.704, P = 0.014), and patients with low risk had better prognosis (P < 0.001 in TCGA; P = 0.038 in GEO). Through ROC analysis, it can be found that this model presented better predictive accuracy for long-term survival. Clinical analyses demonstrated that high-risk group had more advanced N stage, higher risk of metastasis and later pathological stage. Immune-related analysis illustrated that low-risk group had more immune cell infiltration and more activated immune pathways. The pyroptosis-related risk model can be predictive for the survival of COAD patients. That patients with higher risk had poorer prognosis was associated with more advanced tumor stage and higher risk of metastasis, and resulted from highly activated pro-tumor pathways and inhibited immune system and poorer integrity of intestinal epithelial. This study proved the relationship between pyroptosis and immune, which offered basis for future studies.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Humanos , Prognóstico , Piroptose , Microambiente Tumoral/genética
10.
Ann Surg Oncol ; 29(11): 6962-6975, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35723792

RESUMO

BACKGROUND: Adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) after surgery are necessary to reduce the risk of metastasis and recurrence for resectable gastric cancer (GC) patients. Adjuvant CT and CRT have been proven to significantly improve the prognosis for GC patients, when compared with surgery only. However, it is still unclear whether radiotherapy offers additional survival benefits to advanced gastric cancer (AGC) patients. METHODS: PubMed, Cochrane Library, and Embase databases were systematically searched for eligible studies that compared survival benefits between CRT and CT. The endpoints of this meta-analysis were measured as HR for OS or DFS and 95% CI using fixed- or random-effect models. Additionally, side effects, completed rate, and metastatic risk, were calculated as OR. Subgroup analyses according to clinicopathological factors were presented. RESULTS: A total of 28 eligible studies involving 20,220 patients were included in our study. Of these, 17 studies evaluated the survival benefits of additional radiotherapy on overall survival (OS) of gastric cancer patients, ten reported the impact of CRT on disease-free survival (DFS), and 26 studies showed long-term survival rate. The pooled results were significant (HR for OS 0.84, 95% CI 0.71-0.99; HR for DFS 0.76, 95% CI 0.66-0.89). The subgroup analysis showed that adjuvant CRT increased OS for patients without preoperative treatment; showed similar nausea/vomiting, but an increased risk of neutropenia; reduced the risk of locoregional recurrence; failed to improve OS for lymph node (LN)-positive GC patients; and significantly improved prognosis for R1-treated patients. Of note, DFS was improved in all the subgroups via decreasing the locoregional recurrence. CONCLUSION: Compared with CT, adjuvant CRT can improve survival for advanced gastric cancer patients, with similar nausea/vomiting, but increased risk of neutropenia. Patients without preoperative treatment or with positive surgical margins should be strongly recommended to undergo CRT. Treatment regimens should be carefully decided by doctors based on patients' tolerance, physical status, and reaction to treatment. Moreover, CRT improves the DFS for patients regardless of subgroups, because it significantly reduced the risk of locoregional recurrence.


Assuntos
Neutropenia , Neoplasias Gástricas , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Náusea , Recidiva Local de Neoplasia/terapia , Neoplasias Gástricas/cirurgia , Vômito
11.
Oncotarget ; 13: 684-685, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574219

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.14871.].

12.
Exp Biol Med (Maywood) ; 247(2): 131-144, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34617801

RESUMO

Gastric cancer (GC) remains one of the most prevalent types of malignancies worldwide, and also one of the most reported lethal tumor-related diseases. Circular RNAs (circRNAs) have been certified to be trapped in multiple aspects of GC pathogenesis. Yet, the mechanism of this regulation is mostly undefined. This research is designed to discover the vital circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in GC. Expression profiles with diverse levels including circRNAs, miRNAs, and mRNAs were all determined using microarray public datasets from Gene Expression Ominous (GEO). The differential circRNAs expressions were recognized against the published robust rank aggregation algorithm. Besides, a circRNA-based competitive endogenous RNA (ceRNA) interaction network was visualized via Cytoscape software (version 3.8.0). Functional and pathway enrichment analysis associated with differentially expressed targeted mRNAs were conducted using Cytoscape and an online bioinformatics database. Furthermore, an interconnected protein-protein interaction association network which consisted of 51 mRNAs was predicted, and hub genes were screened using STRING and CytoHubba. Then, several hub genes were chosen to explore their expression associated with survival rate and clinical stage in GEPIA and Kaplan-Meier Plotter databases. Finally, a carefully designed circRNA-related ceRNA regulatory subnetwork including four circRNAs, six miRNAs, and eight key hub genes was structured using the online bioinformatics tool.


Assuntos
Bases de Dados de Ácidos Nucleicos , Regulação Neoplásica da Expressão Gênica , RNA Circular , RNA Neoplásico/biossíntese , Software , Neoplasias Gástricas , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , RNA Circular/biossíntese , RNA Circular/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
13.
Biomed Pharmacother ; 144: 112325, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34656065

RESUMO

BACKGROUND: MK8722 is a potent and systemic pan-AMPK activator. It is an effective, direct, allosteric activator of AMPK complex in many mammals. This study tried to explore the underlying anti-cancer molecular mechanism of MK8722 in human pancreatic cancer cells (PCCs). METHODS: The anti-proliferation, invasion and migration functions of MK8722 in human pancreatic cancer analyzed by real time cellular analysis, colony formation assay, cell migration assay, transwell assay and flow cytometery analysis. Moreover, the potential targeted signaling pathway was tested via RNA-seq and pathway enrichment analysis. RESULTS: In the present study, we investigated the anti-PCCs effects of MK8722 on two different human pancreatic cancer cell lines (PANC-1 and Patu8988). The results showed that MK8722 significantly inhibited human tumor cells proliferation and migration/invasion in a dose-dependent manner. Additionally, the influence of MK8722 was examined by analyzing the expression of potential key genes and pathways, which may provide novel insights to the mechanism of MK8722. CONCLUSION: The inhibition of pancreatic cancer by MK8722 through a number of pathways that inhibit carcinoma proliferation, invasion and migration. The potential effect of MK8722 might be determined by regulating the expression of AL162151, IER2, REPIN1, KRT80 to inhibit cycle arrest and migration.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Piridinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Expert Rev Gastroenterol Hepatol ; 15(11): 1329-1336, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34431734

RESUMO

OBJECTIVES: This work aimed to find the association of mixed-type histology and prognosis of T2/T3 GC patients. METHODS: Eligible T2/T3 gastric cancer patients at our institution were identified. The histological types and risk factors affecting OS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 972 T2/T3 gastric cancer patients, including 283 differentiated-type patients, 544 undifferentiated-type patients and 145 mixed type. Mixed-type histology was associated with shorter 5-year OS (DT vs UDT vs MT:57.5% vs 44.9% vs 39.6%, P = 0.002). MT histology can be predictive for prognosis of T2/T3 GC patients (HR for OS: 1.386, 95% CI: 1.028-1.868, P = 0.032), and its malignant potential is not inferior to UDT. In the subgroup analysis, MT can potentially be independent risk factor for non-distal GC patients (P = 0.010). CONCLUSION: This study reported that mixed histology could be regarded as a potential prognostic factor for T2/T3 gastric cancer patients, especially for those with non-distal cancer. MT patients have higher incidence of metastasis and recurrence and had poorer prognosis than those with pure histological type. It is necessary for MT patients to have preoperative pathological examination for accurate histologic classification, so as to make the comprehensive treatment strategies..


Assuntos
Neoplasias Gástricas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
15.
PeerJ ; 9: e10921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34123580

RESUMO

BACKGROUND: Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. METHODS: In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. RESULTS: The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1ß, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. CONCLUSIONS: These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.

16.
Ann Transl Med ; 9(4): 290, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708917

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) that inhibit the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) interactions have shown promising prospects as treatment options for advanced gastric cancer (AGC). This manuscript analyzed well designed clinical trials to evaluate the efficacy and safety of immunotherapy in AGC. METHODS: PubMed, Embase, the Cochrane Library, and Medline were searched for randomized controlled trials (RCTs) of AGC treatments that were published before April 2020. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs) were evaluated to determine the efficacy and safety of ICIs. Network meta-analysis was performed using a random-effects model under the Bayesian framework. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve. RESULTS: Our analysis included five studies having seven immunotherapy regimens and 1,730 patients. The network meta-analysis showed that nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks (88.369%) was the regimen most likely to improve PFS. Nivolumab 3 mg/kg every 3 weeks (84.563%) and nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks (84.556%) were similarly best for OS outcome with excellent tolerance. The regimen of avelumab 10 mg/kg every 2 weeks (91.167%) had the lowest TRAEs. All immunotherapies had similar response rates. CONCLUSIONS: We recommend nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks as the preferred regimen due to their high efficacies.

17.
Mol Cancer ; 20(1): 49, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673851

RESUMO

Neural tumors can generally be divided into central nervous system tumors and peripheral nervous tumors. Because this type of tumor is located in the nerve, even benign tumors are often difficult to remove by surgery. In addition, the majority of neural tumors are malignant, and it is particular the same for the central nervous system tumors. Even treated with the means such as chemotherapy and radiotherapy, they are also difficult to completely cure. In recent years, an increasingly number of studies have focused on the use of mRNA to treat tumors, representing an emerging gene therapy. The use of mRNA can use the expression of some functional proteins for the treatment of genetic disorders or tissue repair, and it can also be applied to immunotherapy through the expression of antigens, antibodies or receptors. Therefore, although these therapies are not fully-fledged enough, they have a broad research prospect. In addition, there are many ways to treat tumors using mRNA vaccines and exosomes carrying mRNA, which have drawn much attention. In this study, we reviewed the current research on the role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors, and examine the future research prospects of mRNA in neural tumors and the opportunities and challenges that will arise in the future application of clinical treatment.


Assuntos
Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/terapia , RNA Mensageiro/genética , Animais , Vacinas Anticâncer , Transformação Celular Neoplásica/metabolismo , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Suscetibilidade a Doenças , Epigênese Genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias do Sistema Nervoso/mortalidade , Especificidade de Órgãos/genética , Prognóstico , Transporte de RNA , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo
18.
BMC Gastroenterol ; 21(1): 15, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407177

RESUMO

BACKGROUND: The number of positive lymph nodes, which was defined as "N stage", is mostly used to predict the survival of D2-resected gastric cancer patients, not the location. A "central lymph node" (CnLN) was defined by Ikoma et al., included common hepatic, celiac and proximal splenic artery LNs. CnLNs located in the extraperigastric area are included in the D2 LN station for gastric cancer. We speculate that CnLNs can be regarded as a predictor of survival. METHODS: Eligible advanced gastric cancer patients who underwent curative resection and D2 lymph node dissection between 2004 and 2012 at our institution were identified. The frequency of CnLN metastases and risk factors affecting DFS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 1178 patients who underwent curative surgery or D2 or more extensive lymphadenectomy. A total of 342 patients had been proven to have CnLN metastasis. Larger tumor size (P < 0.001), more frequent lymphatic vessel invasion (P < 0.001), signet ring cell histology (P = 0.014), and more advanced pathological T stage (P = 0.013) were significantly related to CnLNs metastasis. The patients with CnLN metastasis had a poor prognosis (HR for DFS of 1.366, 95%CI = 1.138-1.640, P = 0.001). For the pN2/3 patients, CnLN metastasis was associated with shorter 5-year DFS (for pN2 patients: 25.9% vs 39.3%, P = 0.017; for pN3 patients: 11.5% vs 23.4%, P = 0.005). CONCLUSION: Gastric cancer patients with CnLN metastasis who underwent D2 resection had a poor prognosis. With the same N stage, the patients with positive CnLNs had shorter survival. CnLNs metastasis could be a supplement to N stage and a predictor of survival in gastric cancer patients. Large sample, multicenter, randomized clinical trials are still needed in the future.


Assuntos
Neoplasias Gástricas , Gastrectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
19.
Clin Res Hepatol Gastroenterol ; 45(1): 101454, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32505731

RESUMO

BACKGROUND: Although many studies have evaluated the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients, the results were conflicting. The objective of this study was to compare clinicopathologic characteristics between SRC type and other types, and evaluate its impact on survival outcome. METHODS: We retrospectively reviewed clinicopathologic and survival data of 1891 patients who underwent curative resection for GC. All patients were divided into differentiated, undifferentiated and SRC type according to the histological classification. The prognostic differences between different types were compared and clinicopathologic factors were analyzed. RESULTS: SRC histology type had a poorer disease-free survival (DFS) than differentiated type (5-year DFS, 37.7% vs 52.2%, P<0.001), but there was no prognostic difference between SRC type and undifferentiated type (37.7% vs 41.9%, P>0.05). For early GC patients, SRC type was more frequent in younger, female patients and T1a stage tumors; the 5-year DFS of SRC type was similar to that of any other histology type (P>0.05). SRC type showed more aggressive biological features, including extensive stomach involvement, large tumor size, advanced pTstage and pN stage, than other types for locally advanced GC patients; poorer DFS was observed in SRC type compared with differentiated type. Multivariate analysis indicated that SRC type (HR:1.71, 95%CI:1.10-1.68, P<0.01) and undifferentiated type (HR:1.21, 95%CI:1.04-1.40, P<0.05) were independently associated with poor DFS in locally advanced GC patients. CONCLUSION: There was a significant difference between early and locally advanced GC patients with regard to clinicopathologic features and prognostic significance of SRC histology. SRC type was an independent prognostic factor for locally advanced GC patients, but not for early GC patients.


Assuntos
Carcinoma de Células em Anel de Sinete , Segunda Neoplasia Primária , Neoplasias Gástricas , Feminino , Humanos , Prognóstico , Estudos Retrospectivos
20.
Front Immunol ; 11: 544563, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193310

RESUMO

Glioblastoma (GBM) is the most malignant form of astrocytoma with short survival and a high recurrence rate and remains a global problem. Currently, surgery, chemotherapy, radiotherapy, and other comprehensive treatments are the main treatment modalities, but patients still have a poor prognosis mainly due to the infiltrative growth of GBM and the protective effect of the blood-brain barrier on tumor cells. Therefore, immunotherapy is expected to be a good option for GBM. In the immune system, different cells play varying roles in the treatment of GBM, so understanding the roles played by various immune cells in treating GBM and considering how to combine these effects to maximize the efficacy of these cells is important for the selection of comprehensive and optimal treatment plans and improving GBM prognosis. Therefore, this study reviews the latest research progress on the role of various types of immune cells in the treatment of GBM.


Assuntos
Barreira Hematoencefálica/imunologia , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Imunoterapia Adotiva , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioblastoma/imunologia , Glioblastoma/mortalidade , Humanos
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