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3.
J Vis Exp ; (207)2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38801272

RESUMO

Gastric cancer is a common heterogeneous tumor. Most patients have advanced gastric cancer at the time of diagnosis and often need chemotherapy. Although 5-fluorouracil (5-FU) is widely used for treatment, its therapeutic sensitivity and drug tolerance still need to be determined, which emphasizes the importance of individualized administration. Pharmacogenetics can guide the clinical implementation of individualized treatment. Single nucleotide polymorphisms (SNPs), as a genetic marker, contribute to the selection of appropriate chemotherapy regimens and dosages. Some SNPs are associated with folate metabolism, the therapeutic target of 5-FU. Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133, dihydrofolate reductase (DHFR) rs1650697 and rs442767, methionine synthase (MTR) rs1805087, gamma-glutamyl hydrolase (GGH) rs11545078 and solute carrier family 19 member 1 (SLC19A1) rs1051298 have been investigated in different kinds of cancers and antifolate antitumor drugs, which have potential forecasting and guiding significance for application of 5-FU. The ion torrent next-generation semiconductor sequencing technology can rapidly detect gastric cancer-related SNPs. Each time a base is extended in a DNA chain, an H+ will be released, causing local pH changes. The ionic sensor detects pH changes and converts chemical signals into digital signals, achieving sequencing by synthesis. This technique has low sample requirement, simple operation, low cost, and fast sequencing speed, which is beneficial for guiding individualized chemotherapy by SNPs.


Assuntos
Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas , Neoplasias Gástricas/genética , Polimorfismo de Nucleotídeo Único/genética , Humanos , Semicondutores , Análise de Sequência de DNA/métodos
4.
Int J Surg ; 109(12): 4162-4172, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37720943

RESUMO

BACKGROUND: The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. METHODS: This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan-Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. RESULTS: Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08-0.57; P =0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56-25.36; P =0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. CONCLUSIONS: Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased post-conversion surgery recurrence.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Gastrectomia/métodos , Receptores ErbB/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-34582329

RESUMO

Strain SJQ9T, an aerobic bacterium isolated from a soil sample collected in Shanghai, PR China, was characterized using a polyphasic approach. It grew optimally at pH 7.0, 30-35 °C and in the presence of 1 % (w/v) NaCl. A comparative analysis of 16S rRNA gene sequences showed that strain SJQ9T fell within the genus Aquabacterium. The closest phylogenetic relatives of strain SJQ9T were Aquabacterium citratiphilum DSM 11900T (98.6 % sequence similarity) and Aquabacterium commune DSM 11901T (96.4 %). Cells of the strain were Gram-stain-negative, motile, non-spore-forming, rod-shaped and positive for oxidase activity and negative for catalase. The chemotaxonomic properties of strain SJQ9T were consistent with those of the genus Aquabacterium: the major fatty acid was summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c). The isoprenoid quinone was Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content was 65.7 mol%. Strain SH9T exhibited a DNA-DNA relatedness level of 34±2 % with A. citratiphilum DSM 11900T and 28±3 % with A. commune DSM 11901T. Based on the obtained data, strain SJQ9T represents a novel species of the genus Aquabacterium, for which the name Aquabacterium soli sp. nov. is proposed. The type strain is SJQ9T (=JCM 33106T=CCTCC AB 2018284T).


Assuntos
Ácidos Graxos , Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Burkholderiales , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/análise , Filogenia , Piretrinas , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
6.
Int J Syst Evol Microbiol ; 68(12): 3902-3907, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30362938

RESUMO

Strain SH9T, an aerobic bacterium isolated from a paddy soil sample collected in Shanghai, China, was characterized using a polyphasic approach. It grew optimally at pH 7.0, temperatures of 30-35 °C and in the presence of 1 % (w/v) NaCl. Comparative analysis of 16S rRNA gene sequences showed that strain SH9T fell within the genus Alsobacter, forming a clear cluster with the type strain of Alsobacter metallidurans, with which it exhibited a 16S rRNA gene sequence similarity value of 98.5 %. Cells of strain SH9T were Gram-stain-negative, motile, non-spore-forming, rod-shaped, positive for catalase and oxidase activity, and negative for atmospheric nitrogen fixation and nitrate reduction. The strain was a chemo-organotrophic bacterium, incapable of growth on C1 substrates. The chemotaxonomic properties of strain SH9T were consistent with those of the genus Alsobacter: the predominant ubiquinone was Q-10, and the major fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and phosphatidylmonomethylethanolamine. The DNA G+C content was 68.5 mol%. Strain SH9T exhibited a DNA-DNA relatedness level of 20±2 % with A. metallidurans NBRC 107718T. Based on the data obtained, strain SH9T represents a novel species of the genus Alsobacter, for which the name Alsobactersoli sp. nov. is proposed. The type strain is SH9T (=JCM 32501T=CCTCC AB 2017284T). A new family, Alsobacteraceae fam. nov., is also proposed encompassing strain SH9T and Alsobacter metallidurans NBRC 107718T.


Assuntos
Alphaproteobacteria/classificação , Filogenia , Microbiologia do Solo , Alphaproteobacteria/genética , Alphaproteobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Oryza , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/análogos & derivados , Ubiquinona/química
7.
Biochem Biophys Res Commun ; 505(2): 426-431, 2018 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-30266402

RESUMO

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a metabolic bone disease caused by unbalance between osteoblast bone formation and osteoclast bone resorption. In this study, the moderating effect of DGCR5 on osteogenic differentiation and its role in PMOP was assessed. METHODS: The expression levels of DGCR5, miR-30d-5p, and Runt-related transcription factor 2 (Runx2) mRNA and protein were determined by qRT-PCR and western blot, separately. The bone marrow human mesenchymal stem cells (hMSCs) were isolated from bone marrow of patients with PMOP or the healthy control. ALP activity and bone mineral density (BMD) were detected to reflect the osteogenic differentiation status. RIP and RNA pull-down assay were performed to explore the combination and interaction between DGCR5 and miR-30d-5p. RESULTS: Compared with the healthy control group (n = 20), DGCR5 was down-regulated in hMSCs from patients with PMOP (n = 20). Overexpression of DGCR5 induced osteogenic differentiation of hMSCs. DGCR5 up-regulated the expression of Runx2 through miR-30d-5p. DGCR5 up-regulated the expression of Runx2 through miR-30d-5p to induce osteogenic differentiation of hMSCs. CONCLUSION: DGCR5 negatively regulates miR-30d-5p, and it up-regulates Runx2 through miR-30d-5p, thereby inducing osteogenic differentiation of hMSCs, which may help to delay PMOP development.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , MicroRNAs/metabolismo , Osteogênese , RNA Longo não Codificante/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Osteoblastos/citologia , Osteoporose Pós-Menopausa/etiologia , RNA Longo não Codificante/genética
8.
Cell Death Dis ; 8(4): e2736, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28383563

RESUMO

Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. AJAP1 overexpression inhibited HCC progression and metastasis, while its silencing had the opposite effect both in vitro and in vivo. Furthermore, AJAP1 blocked epithelial-to-mesenchymal transition by interacting with ß-catenin and inhibiting its nuclear translocation, which suppressed zinc finger E-box binding homeobox 1 (ZEB1) transcription. These results indicate that AJAP1 inhibits HCC metastasis, and is thus a potential therapeutic target for HCC treatment.


Assuntos
Carcinoma Hepatocelular/metabolismo , Moléculas de Adesão Celular/biossíntese , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/biossíntese , Transdução de Sinais , Homeobox 1 de Ligação a E-box em Dedo de Zinco/biossíntese , beta Catenina/biossíntese , Transporte Ativo do Núcleo Celular/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas de Neoplasias/genética , Transcrição Gênica , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , beta Catenina/genética
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