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1.
Anal Chem ; 96(10): 4213-4223, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427460

RESUMO

The accurate quantification of cancer-derived exosomes, which are emerging as promising noninvasive biomarkers for liquid biopsies in the early diagnosis of cancer, is becoming increasingly imperative. In our work, we developed a magnetically controlled photothermal, colorimetric, and fluorescence trimode aptasensor for human gastric cancer cell (SGC-7901)-derived exosomes. This sensor relied on CP/Mn-PBA DSNBs nanocomposites, created by decorating copper peroxide (CP) nanodots on polyethyleneimine-modified manganese-containing Prussian blue analogues double-shelled nanoboxes (PEI-Mn-PBA DSNBs). Through self-assembly, we attached CD63 aptamer-labeled CP/Mn-PBA DSNBs (Apt-CP/Mn-PBA DSNBs) to complementary DNA-labeled magnetic beads (cDNA-MB). During exosome incubation, these aptamers preferentially formed complexes with exosomes, and we efficiently removed the released CP/Mn-PBA DSNBs by using magnetic separation. The CP/Mn-PBA DSNBs exhibited high photoreactivity and photothermal conversion efficiency under near-infrared (NIR) light, leading to temperature variations under 808 nm irradiation, correlating with different exosome concentrations. Additionally, colorimetric detection was achieved by monitoring the color change in a 3,3',5,5'-tetramethylbenzidine (TMB) system, facilitated by PEI modification, NIR-enhanced peroxidase-like activity of CP/Mn-PBA DSNBs and their capacity to generate Cu2+ and H2O2 under acidic conditions. Moreover, in the presence of Cu2+ and ascorbic acid (AA), DNA sequences could form dsDNA-templated copper nanoparticles (CuNPs), which emitted strong fluorescence at around 575 nm. Increasing exosome concentrations correlated with decreases in temperature, absorbance, and fluorescence intensity. This trimode biosensor demonstrated satisfactory ability in differentiating gastric cancer patients from healthy individuals using human serum samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Cobre , Peróxidos , Peróxido de Hidrogênio , Colorimetria
2.
IET Syst Biol ; 18(2): 41-54, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38377622

RESUMO

BACKGROUND: Gastric cancer (GC) is a frequent malignancy of the gastrointestinal tract. Exploring the potential anoikis mechanisms and pathways might facilitate GC research. PURPOSE: The authors aim to determine the significance of anoikis-related genes (ARGs) in GC prognosis and explore the regulatory mechanisms in epigenetics. METHODS: After describing the genetic and transcriptional alterations of ARGs, we searched differentially expressed genes (DEGs) from the cancer genome atlas and gene expression omnibus databases to identify major cancer marker pathways. The non-negative matrix factorisation algorithm, Lasso, and Cox regression analysis were used to construct a risk model, and we validated and assessed the nomogram. Based on multiple levels and online platforms, this research evaluated the regulatory relationship of ARGs with GC. RESULTS: Overexpression of ARGs is associated with poor prognosis, which modulates immune signalling and promotes anti-anoikis. The consistency of the DEGs clustering with weighted gene co-expression network analysis results and the nomogram containing 10 variable genes improved the clinical applicability of ARGs. In anti-anoikis mode, cytology, histology, and epigenetics could facilitate the analysis of immunophenotypes, tumour immune microenvironment (TIME), and treatment prognosis. CONCLUSION: A novel anoikis-related prognostic model for GC is constructed, and the significance of anoikis-related prognostic genes in the TIME and the metabolic pathways of tumours is initially explored.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Prognóstico , Anoikis/genética , Algoritmos , Biomarcadores , Microambiente Tumoral/genética
3.
Anal Biochem ; 688: 115472, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38266666

RESUMO

Due to the late detection of stomach cancer, this cancer usually causes high mortality. The development of an electrochemical genosensor to measure microRNA 106b (miR-106b), as a gastric cancer biomarker, is the aim of this effort. In this regard, first, 1,3,5-benzenetricarboxylate (BTC) metal-organic frameworks (Zn-BTC MOF) were self-assembled on the glassy carbon electrode and then the probe (ssDNA) was immobilized on it. The morphology Zn-BTC MOF was characterized by SEM, FT-IR, Raman and X-Ray techniques. Zn-BTC MOF as a biosensor substrate has strong interaction with ssDNA. Quantitative measurement of miR-106b was performed by electrochemical impedance spectroscopy (EIS). To perform this measurement, the difference of the charge transfer resistances (ΔRct) of Nyquist plots of the ssDNA probe modified electrode before and after hybridization with miR-106b was obtained and used as an analytical signal. Using the suggested genosensor, it is possible to measure miR-106b in the concentration range of 1.0 fM to 1.0 µM with a detection limit of 0.65 fM under optimal conditions. Moreover, at the genosensor surface, miR-106b can be detected from a non-complementary and a single base mismatch sequence. Also, the genosensor was used to assess miR-106b in a human serum sample and obtained satisfactory results.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Técnicas Biossensoriais/métodos , DNA de Cadeia Simples/genética , MicroRNAs/genética , Zinco , Técnicas Eletroquímicas/métodos , Limite de Detecção
4.
BMC Gastroenterol ; 23(1): 440, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097952

RESUMO

BACKGROUND: Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. METHODS: The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011-2022 were retrospectively analyzed. RESULTS: The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed. CONCLUSION: Type 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.


Assuntos
Tumores Neuroendócrinos , Neoplasias Gástricas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia
5.
Stud Health Technol Inform ; 308: 155-167, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38007737

RESUMO

Gastric cancer is a malignant tumor with high incidence and death rate. Every year, Approximately 950,000 new cases of gastric cancer occur globally with nearly 700000 deaths,so gastric precancerous lesions(GPL) was crucial and important.At present, the effective diagnostic methods for gastric precancerous lesions are generally gastroscope and pathological changes of gastric mucosal, but those methods were invasive and would bring some pains to patients and not suitable for frequent and large-scale screening of gastric cancer or GPL.This study aimed to look for a sensitive,effective and non-invasive diagnostic method to improve the early diagnosis rate of GLP, and thereby reduce the incidence and death rate of gastric cancer.Tongue diagnosis is one of the classic diagnostic methods in traditional Chinese medicine(TCM).The tongue was closely related to the spleen and stomach.In the study, we collected 133 patients with chronic gastritis, including 53 cases in inflammatory group, 31 cases in atrophic group, and 49 cases in intestinal metaplasia group. and we analyzed the correlation between tongue,microbiota of tongue coating and clinical symptoms of GLP.The results showed that greasy coating was closely related to the intestinal metaphase of patients, indicating that greasy coating was closed link with intestinal metaphase phase of patients.Abundance of 209 genus were significant differences between greasy and non-greasy coating in intestinal metaphase phase of patients, Top10 were Streptococcus,norank_p__Saccharibacteria,Alloprevotella, Atopobium, Megasphaera, Gemella, Moraxella,unclassified_f__Prevotellaceae, Solobacterium and Stomatobaculum. Alloprevotella and Streptococcus were important genus markers and Alloprevotella was selected as a potential oral biomarker to diagnose intestinal metaphase phase of patients, the AUC value is 0.74.


Assuntos
Gastrite , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Gastrite/diagnóstico , Gastrite/microbiologia , Gastrite/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Metáfase , Biomarcadores , Lesões Pré-Cancerosas/microbiologia
6.
Biomark Med ; 17(16): 679-691, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37934044

RESUMO

The progression of any disease and its outcomes depend on the complicated interaction between pathogens, host and environmental factors. Thus, complete knowledge of bacterial toxins involved in pathogenesis is necessary to develop diagnostic methods and alternative therapies, including vaccines. This review summarizes recently employed biomarkers to diagnose the presence of Helicobacter pylori bacteria. The authors review distinct types of disease-associated biomarkers such as urease, DNA, miRNA, aptamers and bacteriophages that can be utilized as targets to detect Helicobacter pylori and, moreover, gastric cancer in its early stage. A detailed explanation is also given in the context of the recent utilization of these biomarkers in the development of a highly specific and sensitive biosensing platform.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Helicobacter pylori/genética , Neoplasias Gástricas/diagnóstico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/complicações , Biomarcadores
7.
Altern Ther Health Med ; 29(8): 302-309, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37632952

RESUMO

Objective: To explore the results of lymph node metastasis in patients with gastric cancer in a real-world setting. Methods: Patients (n = 272) who underwent radical gastrectomy with lymph node dissection for gastric cancer from November 2017 to August 2019 at Huzhou Central Hospital, China. The main outcome was the lymph node metastasis rate. The chi-square test was used to compare categorical variables. Binary logistic regression analysis was used to examine the relationship between risk factors and lymph node metastasis in gastric cancer and early gastric cancer. In multivariate analysis, OR and 95% CI were calculated to evaluate the risk. Statistical significance was defined as P < .05. Statistical analysis was performed using SPSS software version 26.0 (SPSS Inc.) and GraphPad PRISM 9.0. Results: Among the 272 patients who underwent surgery, 143 (52.6%) had lymph node metastasis. The proportion of female patients was higher in those under 40 years of age. The incidence of gastric cancer was highest in the lesser curvature of the gastric antrum. The lymph node metastasis rates were 5.3%, 25%, 39%, 78.1%, and 76.8% for invasion to the mucosal layer, submucosal layer, muscular layer, serosal layer, and beyond the serosal layer, respectively. There was a statistically significant difference in lymph node metastasis between invasion to the mucosal layer and the other four layers (P < .05), while there was no statistically significant difference between invasion to the submucosal and muscular layers (P > .05) and between invasion to the serosal layer and beyond (P > .05). Well-differentiated gastric cancer had almost no lymph node metastasis (0%), while moderately differentiated gastric cancer had a lower rate of lymph node metastasis (32%), and there was no statistically significant difference between the two. The lymph node metastasis rates were higher for poorly differentiated adenocarcinoma (66.7%), mucinous adenocarcinoma (63.6%), and signet ring cell carcinoma (57.1%), and there was no statistically significant difference between the three. Conclusion: Lymph node metastasis in gastric cancer is related to the depth of invasion and pathological subtype, and is not related to age, sex, or tumor location.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Metástase Linfática , Excisão de Linfonodo , Adenocarcinoma/patologia , Fatores de Risco
8.
OMICS ; 27(6): 260-272, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37229622

RESUMO

Gastric cancer (GC) is among the leading causes of cancer-related deaths worldwide. The discovery of robust diagnostic biomarkers for GC remains a challenge. This study sought to identify biomarker candidates for GC by integrating machine learning (ML) and bioinformatics approaches. Transcriptome profiles of patients with GC were analyzed to identify differentially expressed genes between the tumor and adjacent normal tissues. Subsequently, we constructed protein-protein interaction networks so as to find the significant hub genes. Along with the bioinformatics integration of ML methods such as support vector machine, the recursive feature elimination was used to select the most informative genes. The analysis unraveled 160 significant genes, with 88 upregulated and 72 downregulated, 10 hub genes, and 12 features from the variable selection method. The integrated analyses found that EXO1, DTL, KIF14, and TRIP13 genes are significant and poised as potential diagnostic biomarkers in relation to GC. The receiver operating characteristic curve analysis found KIF14 and TRIP13 are strongly associated with diagnosis of GC. We suggest KIF14 and TRIP13 are considered as biomarker candidates that might potentially inform future research on diagnosis, prognosis, or therapeutic targets for GC. These findings collectively offer new future possibilities for precision/personalized medicine research and development for patients with GC.


Assuntos
Biomarcadores Tumorais , Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/genética , Redes Reguladoras de Genes , Medicina de Precisão , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Biologia Computacional/métodos , Aprendizado de Máquina , ATPases Associadas a Diversas Atividades Celulares/genética , Proteínas de Ciclo Celular/genética
9.
Cancer Treat Res ; 188: 89-104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38175343

RESUMO

The occurrence of gastric cancer has been associated with an increased risk of lobular breast tumors in a subset of patients harboring selected germline mutations. Among all, the germline alteration of the gene coding for E-Cadherin (CDH1) was associated with an increased risk of gastric cancer diffuse-histotype and lobular breast cancer. However, the risk assessment of breast neoplasms and the role of multiple prophylactic procedures in these patients has never been systematically addressed. In addition, the performance of the common screening procedures for lobular breast cancer like mammography is suboptimal. Therefore, recalling the need for a better articulation of the patient-centered strategies of surveillance for individuals with germline CDH1 and other similar alterations, to offer comprehensive approaches for prevention, early diagnosis, and treatment. Accordingly, this chapter aims to discuss the value and the role of integrated oncological care in the era of oncology sub-specializations. Additionally, it sheds light on how the harmonization across the health providers can enhance patient care in this setting.


Assuntos
Neoplasias da Mama , Oncologia Integrativa , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Mama , Oncologia
10.
Clin Transl Gastroenterol ; 13(11): e00531, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113027

RESUMO

INTRODUCTION: Family history of gastric cancer has been shown as an independent risk factor of gastric cancer development and is associated with increased risk of progression to gastric cancer among patients with gastric intestinal metaplasia (GIM). METHODS: Between 2017 and 2020, we conducted a prospective pilot screening program of patients with a confirmed first-degree relative with gastric cancer to evaluate the feasibility of screening and prevalence of precursor lesions (e.g., GIM or dysplasia) on biopsy. RESULTS: A total of 61 patients completed screening by upper endoscopy with a mapping biopsy protocol: 27 (44%) were found to have GIM and 4 (7%) were found with low-grade dysplasia. DISCUSSION: Our pilot screening program identified a high prevalence of precursor lesions for gastric cancer among asymptomatic patients with a first-degree relative with gastric cancer. Careful endoscopic inspection and standardized biopsy protocols may aid in prompt identification of these precursor lesions in those at risk of gastric cancer.


Assuntos
Prestação Integrada de Cuidados de Saúde , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Projetos Piloto , Estudos Prospectivos , Detecção Precoce de Câncer , Metaplasia , Gastroscopia/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/epidemiologia
11.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(3): 204-207, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-34645162

RESUMO

Peritoneal metastasis is the most common distant metastasis of gastric cancer. As an end-stage event of gastric cancer, patients with peritoneal metastasis often have lost the chance of radical resection, and even after palliative surgical resection, the long-term outcomes are still not satisfactory. In recent years, with the application and promotion of laparoscopic technology, neoadjuvant intraperitoneal and systemic chemotherapy, hyperthermic intraperitoneal chemotherapy and cytoreductive surgery, through perioperative comprehensive treatment strategies by multidisciplinary team, the quality of life and survival of patients with peritoneal metastasis have been significantly improved. Some patients with gastric cancer peritoneal metastasis diagnosed by laparoscopy even get the opportunity to have radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after neoadjuvant intraperitoneal and systemic chemotherapy. Taking into account the progress in the treatment of gastric cancer peritoneal metastasis in recent years, this article intends to combine current clinical evidence and to discuss the key issues in the course of clinical diagnosis and treatment of gastric cancer peritoneal implantation and metastasis, including the imaging diagnosis of peritoneal metastasis, laparoscopic examination, evaluation of peritoneal metastasis and comprehensive treatment plan.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/terapia , Peritônio , Qualidade de Vida , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia
12.
BMJ Case Rep ; 14(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975851

RESUMO

A 62-year-old woman was referred to our department for further investigation of anaemia. Blood test showed macrocytic anaemia. Oesophagogastroduodenoscopy (OGD) revealed proximal-predominant gastric atrophy and flat elevated lesion in the gastric body. Several days after OGD, she complained of gait disturbance and was diagnosed with subacute combined degeneration of the spinal cord. Furthermore, laboratory tests showed positive for both anti-parietal cell and anti-intrinsic factor antibodies, as well as increased serum gastrin level and decreased pepsinogen I level, which confirmed the diagnosis of autoimmune gastritis (AIG). Anaemia and neurological symptoms were improved after vitamin B12 supplementation. Subsequently, the patient underwent gastric endoscopic submucosal dissection; histopathological examination revealed gastric adenoma. AIG can cause gastric neoplasms and vitamin B12 deficiency, with the latter resulting in pernicious anaemia and neurological disorders. These diseases are treatable but potentially life-threatening. This case highlights the importance of early diagnosis of AIG and proper management of its comorbidities.


Assuntos
Adenoma , Doenças Autoimunes , Gastrite , Neoplasias Gástricas , Degeneração Combinada Subaguda , Deficiência de Vitamina B 12 , Adenoma/patologia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/patologia , Feminino , Gastrite/complicações , Gastrite/diagnóstico , Gastrite/patologia , Humanos , Pessoa de Meia-Idade , Medula Espinal/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico
13.
Int J Biol Sci ; 17(7): 1629-1643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994849

RESUMO

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) plays important roles in the pathogenesis and progression of cancers. However, the role of SNHG12 in the metastasis of gastric cancer (GC) has not yet been thoroughly investigated. In the present study, we demonstrated that SNHG12 was upregulated in GC tissues and cell lines. In addition, the expression level of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM stage and lymph node metastasis and was associated with disease-free survival (DFS) and overall survival (OS) in GC patients. In vivo and in vitro assays indicated that SNHG12 promotes GC metastasis and epithelial-mesenchymal transition (EMT). Bioinformatics and mechanistic analyses revealed that SNHG12 can directly target miR-218-5p to regulate YWHAZ mRNA, forming an SNHG12/miR-218-5p/YWHAZ axis and decreasing the ubiquitination of ß-catenin. In addition, SNHG12 stabilizes CTNNB1 mRNA by binding with HuR, thus activating the ß-catenin signaling pathway. Further analysis also revealed that the transcription factor YY1 negatively modulates SNHG12 transcription. In conclusion, SNHG12 is a potential prognostic marker and therapeutic target for GC. Negatively modulated by YY1, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and stabilizing CTNNB1 via activation of the ß-catenin signaling pathway.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Regulação para Cima , Fator de Transcrição YY1/genética , Idoso , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , RNA Longo não Codificante/biossíntese , RNA Neoplásico/genética , Estudos Retrospectivos , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/secundário , Fator de Transcrição YY1/biossíntese
14.
BMC Cancer ; 21(1): 551, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992091

RESUMO

BACKGROUND: Peripheral blood leukocyte (PBL) DNA methylation may serve as a surrogate marker to evaluate the susceptibility to and prognosis of gastric cancer (GC). In this study, blood-derived DNA methylation levels of two tumour-related genes, namely, ZNF331 and WIF1, and their impacts on the risk and prognosis of GC were evaluated. METHODS: In total, 398 GC cases and 397 controls were recruited for the study. Then, all cases were followed up for 5 years. ZNF331 and WIF1 promoter methylation status in PBLs was measured using a methylation-sensitive high-resolution melting method. Logistic and Cox regression models were used to analyse the correlation between gene methylation and the risk and prognosis of GC. Confounders were balanced through propensity score (PS) matching. RESULTS: High ZNF331 methylation significantly decreased GC risk after PS adjustment (OR = 0.580, 95% CI: 0.375-0.898, P = 0.015), which also presented in males (OR = 0.577, 95% CI: 0.343-0.970, P = 0.038). However, WIF1 methylation was not associated with GC risk. Additionally, significant combined effects between ZNF331 methylation and the intake of green vegetables and garlic were observed (OR = 0.073, 95% CI: 0.027-0.196, P < 0.001 and OR = 0.138, 95% CI: 0.080-0.238, P < 0.001, respectively). Furthermore, ZNF331 and WIF1 methylation had no impact on the prognosis of GC. CONCLUSION: ZNF331 methylation in PBLs may affect GC risk in combination with the consumption of green vegetables and garlic and may act as a potential biomarker of GC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Neoplasias Gástricas/epidemiologia , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/metabolismo , Inquéritos sobre Dietas/estatística & dados numéricos , Epigênese Genética , Feminino , Alho , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo , Prognóstico , Regiões Promotoras Genéticas/genética , Pontuação de Propensão , Fatores de Proteção , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/prevenção & controle , Verduras
15.
Cell Mol Biol Lett ; 26(1): 12, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794762

RESUMO

BACKGROUND: The purpose of this study was to explore the clinical value of miR-378c and its target gene YY1 in gastric cancer. METHODS: The TCGA database was employed to analyse miR-378c expression in gastric cancer. qRT-PCR was applied to identify miR-378c and YY1 in tissues and serum of patients suffering from gastric cancer. The association of miR-378c with the clinical data of patients with gastric cancer was analysed. Receiver operating characteristics (ROC) curve analysis was used to determine the diagnostic value of miR-378c and YY1 in gastric cancer, and analyse the relationship between miR-378c and YY1 and patients' survival. Pearson's test was applied to determine the association between miR-378c and YY1 in tissue and serum of patients. Dual-Luciferase Reporter assay was employed to examine the targeting association between miR-378c and YY1. Finally, independent prognostic factors was determined in patients with gastric cancer using Cox regression analysis. RESULTS: In the TCGA database, miR-378c was weakly expressed in gastric cancer. Overall, patients with low expression had a lower survival rate. The expression of miR-378c decreased and the expression of YY1 increased in cancer tissues and serum of tumour patients. In patients with low expression of miR-378c the tumour size was ≥ 5 cm. Low differentiation, high TNM staging and lymph node invasion rate increased significantly, but the 5-year survival rate decreased in the patients. miR-378c and YY1 had better diagnostic value in gastric cancer. TargetScan, miRDB, starBase and miRTarBase predicted that YY1 was a potential gene of miR-378c, and the Dual-Luciferase Reporter assay revealed that there was a targeting relationship between the two, which was proved by correlation analysis. Multivariate Cox analysis revealed that differentiation, TNM staging and miR-378c were independent prognostic factors for patients. CONCLUSIONS: MiR-378c is weakly expressed in gastric cancer patients and may be considered as a promising diagnostic and prognostic indicator for gastric cancer.


Assuntos
MicroRNAs/metabolismo , Neoplasias Gástricas/diagnóstico , Fator de Transcrição YY1/metabolismo , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Factuais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , MicroRNAs/sangue , MicroRNAs/química , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Fator de Transcrição YY1/química , Fator de Transcrição YY1/genética
16.
Future Oncol ; 17(19): 2431-2438, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33764163

RESUMO

Limited data are available regarding the efficacy of nutrition support in advanced gastric cancer (AGC) patients receiving a standard second-line combination chemotherapy. The BALAST study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for patients with AGC treated with ramucirumab plus taxane as second-line treatment. As part of the routine care, patients who are malnourished or at risk of malnutrition will receive nutrition support from dietitians. We will enroll a total of 26 patients to estimate weight control rate at 12 weeks as primary end point. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients receiving second-line chemotherapy.


Lay abstract Various guidelines recommend that nutrition support therapy should be considered if cancer patients are malnourished or at risk of malnutrition. Several studies have revealed that body weight loss, which is an important factor in determining the nutrition status, may predict survival during second-line standard chemotherapy with ramucirumab and a taxane for advanced gastric cancer (AGC) patients. However, limited data are available regarding the efficacy of nutrition support in AGC patients receiving ramucirumab and a taxane. This study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for Japanese patients with AGC treated with ramucirumab and a taxane. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients in second-line treatment. Clinical trial registration: UMIN000037867.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desnutrição/terapia , Neoplasias Gástricas/tratamento farmacológico , Adulto , Manutenção do Peso Corporal/efeitos dos fármacos , Seguimentos , Humanos , Masculino , Desnutrição/diagnóstico , Desnutrição/etiologia , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Terapia Nutricional , Estado Nutricional/efeitos dos fármacos , Estudos Observacionais como Assunto , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Ramucirumab
17.
Pharmacol Res ; 165: 105411, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401002

RESUMO

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.


Assuntos
Adenocarcinoma/diagnóstico , Antineoplásicos/uso terapêutico , Misturas Complexas/uso terapêutico , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/metabolismo , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Análise Serial de Tecidos , Trametes , Resultado do Tratamento
18.
J Cancer Policy ; 28: 100277, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-35559906

RESUMO

BACKGROUND: The aim of this study was to identify the time intervals between the demand for health services and the initiation of cancer treatment, and to explore the associated factors, in gastric cancer patients being treated in an oncology hospital in northern Brazil. METHODS: This cross-sectional study. Gastric cancer patients receiving treatment in a northern Brazil reference hospital were interviewed. A Mann-Whitney test was used to verify associations between the time intervals of access to treatment and socioeconomic factors, clinical variables, and patient difficulties, adopting a 0.05 significance level. RESULTS: The average time intervals were 471.3 days between symptom onset and primary health service request and 180.9 days between diagnosis and treatment. The average time between the onset of symptoms and the treatment of gastric cancer was 747.8 days. Patients using herbal home remedies showed the longest times before seeking primary health care (p = 0.04). Delays between diagnosis and treatment were associated with unemployment (p = 0.03). High average times until oncologist appointments were related to the absence of comorbidities (p = 0.004). Personal difficulties and a lack of hospital beds were associated with long time intervals to specialist appointments and between diagnosis and treatment. Personal difficulties were associated with long time intervals between the onset of symptoms and the treatment of gastric cancer. CONCLUSION: Gastric cancer patients faced delays and healthcare access barriers in a region with high mortality for this disease. Appropriate interventions are necessary to reduce delays and better control the disease. POLICY SUMMARY: In this paper we have explored the barriers to access to diagnosis and treatment for patients with gastric cancer in a major cancer centre in Northern Brazil. The results will inform strategies for improving timely access to critical cancer services.


Assuntos
Neoplasias Gástricas , Brasil/epidemiologia , Estudos Transversais , Diagnóstico Tardio , Acessibilidade aos Serviços de Saúde , Humanos , Neoplasias Gástricas/diagnóstico
19.
Clin Nucl Med ; 46(1): 1-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33181743

RESUMO

PURPOSE: The aim was to explore whether baseline total lesion glycolysis (TLG) can improve the prognostic value of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients treated with an R-CHOP-like regimen. MATERIALS AND METHODS: Ninety-four PG-DLBCL patients who underwent baseline PET/CT between July 2010 and May 2019 were included in this retrospective study. FDG-avid lesions in each patient were segmented to calculate the SUVmax, total metabolic tumor volume (TMTV), and TLG. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate prognosis. RESULTS: During the follow-up period of 5 to 108 months (35.3 ± 23.5 months), high TLG and a high NCCN-IPI were significantly associated with poor PFS and OS. Total lesion glycolysis and the NCCN-IPI were independent predictors of PFS and OS. Patients were stratified into 3 groups according to the combination of TLG and the NCCN-IPI for PFS (P < 0.001) and OS (P < 0.001): high-risk group (TLG > 1159.1 and NCCN-IPI 4-8) (PFS and OS, 57.7% and 61.5%, respectively, n = 42), intermediate-risk group (TLG > 1159.1 or NCCN-IPI 4-8) (PFS and OS, both 76.9%, n = 26), and low-risk group (TLG ≤ 1159.1 and NCCN-IPI 0-3) (PFS and OS, 97.6% and 100.0%, respectively, n = 26). CONCLUSIONS: Both TLG and the NCCN-IPI are independent predictors of PG-DLBCL patient survival. Moreover, the combination of TLG and the NCCN-IPI improved patient risk stratification and might help personalize therapeutic regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Glicólise/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo , Vincristina/farmacologia , Vincristina/uso terapêutico
20.
Biol Pharm Bull ; 43(10): 1476-1480, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999157

RESUMO

Various sources of information are available for identifying and evaluating adverse drug reactions (ADRs). However, some studies only used the ADR data from spontaneous reporting databases to evaluate the safety of post-marketing drugs. This study was performed to identify an appropriate method for evaluating the safety of post-marketing drugs by comparing the frequencies of ADRs among three datasets: randomized controlled trials, published case reports, and spontaneous reports. Taking ADR data for fluorouracil as an example, we collected the three types of data and extracted their ADR information. All listed ADRs were sorted by frequency from high to low, and the top five ADRs were chosen from each dataset. We assigned an index value of 1.0 to the frequency of one specific ADR (diarrhea) and then calculated the index values of the other ADRs relative to diarrhea. Ten different ADRs were mentioned in the top five ADRs of the three datasets, and only diarrhea and nausea/vomiting were included in all three datasets. The rank orders of the top five ADRs varied among the three datasets. Nausea and vomiting was the most frequent ADR in all three datasets; the remaining ADRs differed among the datasets. There were significant differences in the recording of ADRs and the frequency distributions among the three datasets. A comprehensive and reliable safety profile for post-marketing drugs should not be based on any one source. Spontaneous reports from monitoring institutions provided the most ADR data. Randomized controlled trials and case reports published in the literature can supplement the results from spontaneous reports.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antimetabólitos Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Fluoruracila/efeitos adversos , Armazenamento e Recuperação da Informação/estatística & dados numéricos , Neoplasias Gástricas/tratamento farmacológico , Bases de Dados Factuais/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia
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