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1.
Ther Adv Med Oncol ; 16: 17588359241229425, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322753

RESUMO

Background: Due to the complex histological type and anatomical structures, there has been considerable debate on the classification of adenocarcinoma of the esophagogastric junction (AEG), especially Siewert II AEG. Furthermore, neither the American Joint Committee on Cancer (AJCC) 7th tumor-node-metastasis (TNM) [esophageal adenocarcinoma (E) or gastric cancer (G)] nor the AJCC 8th TNM (E or G) accurately predicted the prognosis of patients with Siewert II AEG. Objective: This study aimed to investigate the factors influencing the survival and prognosis of patients with Siewert II AEG and establish a new and better prognostic predictive model. Design: A retrospective study. Methods: Patients with Siewert II AEG, retrieved from the Surveillance, Epidemiology, and End Results (SEER) databases, were assigned to the training set. Patients retrieved from a single tertiary medical center were assigned to the external validation set. Significant variables were selected using univariate and multivariate Cox regression analyses to construct the nomogram. Nomogram models were assessed using the concordance index (C-index), a calibration plot, decision curve analysis (DCA), and external validation. Results: Age, tumor grade, and size, as well as the T, N, and M stages, were included in the nomograms. For the SEER training set, the C-index of the nomogram was 0.683 (0.665-0.701). The C-index of the nomogram for the external validation set was 0.690 (0.653-0.727). The calibration curve showed good agreement between the nomogram estimations and actual observations in both the training and external validation sets. The DCA showed that the nomogram was clinically useful. Conclusion: The new predictive model showed significant accuracy in predicting the prognosis of Siewert II AEG.

2.
Surg Obes Relat Dis ; 20(5): 467-481, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38151417

RESUMO

BACKGROUND: With the rising prevalence of severe obesity, bariatric surgery has emerged as a crucial treatment option. As the number of surgeries performed worldwide increases, there has been growing interest in the impact of bariatric surgery on cancer incidence. While several studies have examined this relationship, the topic remains controversial. OBJECTIVES: We conducted this systematic review of cohort studies with meta-analysis to evaluate the effect of bariatric surgery versus nonsurgical treatment on overall cancer incidence. However, the effects may vary when focusing on specific cancer types, surgical procedures, or gender, so we conducted additional subgroup analyses. SETTING: A meta-analysis. University hospital. METHODS: The Cochrane, Embase, PubMed, and Web of Science databases were searched for studies from 1 January 2000 to 1 December 2022. Meta-analysis was conducted to evaluate the pooled effect and further implemented subgroup analysis stratified by cancer type, operation type, and sex. RESULTS: All cohort studies were included in this meta-analysis from 18,216 studies. The overall cancer incidence demonstrated a significant decrease in the group with bariatric surgery (odds ratios [OR] = .56, P = .000, 95% CI .46 to .68). In subgroup analysis, similar decrease effect was found in 9 cancers. Furthermore, the incidence of cancer decreased significantly in male (OR = .66, P = .001, 95% CI .51 to .85) and female patients (OR = .63, P = .000, 95% CI .57 to .69) and patients undergoing gastric bypass (OR = .46, P = .000, 95% CI .33 to .63) or sleeve gastrectomy (OR = .44, P = .001, 95% CI .27 to .70). CONCLUSIONS: In the overall analysis, bariatric surgery could reduce the incidence of cancer significantly. Further large-scale well-matched studies are needed to verify the protective effect of bariatric surgery on cancer incidence.


Assuntos
Cirurgia Bariátrica , Neoplasias , Obesidade Mórbida , Humanos , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/estatística & dados numéricos , Incidência , Neoplasias/epidemiologia , Neoplasias/cirurgia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/complicações , Masculino , Feminino , Estudos de Coortes
3.
Therap Adv Gastroenterol ; 16: 17562848231211543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026103

RESUMO

Background: Gastric cancer (GC) is one of the common and fatal cancers. Even though the Tumor, Node, Metastasis (TNM) staging system is the most classical staging system recognized worldwide, it has been controversial because there are various factors affecting the prognosis of GC patients. Objectives: The study aims to evaluate the relationship between interleukin-6 (IL-6) and several clinical indicators and construct a prognostic model to better predict the prognosis of GC. Design: A retrospective study. Methods: Data of 249 patients with GC diagnosed in GC center of West China Hospital were collected. Clinicopathological characteristics were analyzed to determine whether there were differences between IL-6 HIGH group and IL-6 LOW group. Besides, the association between the two groups and tumor marker levels was clarified. The K-M curves of 3- and 5-year were plotted with log-rank test. Afterward, we conducted univariate and multivariate analysis and a predicting nomogram. Significantly, C-index, and calibration were used to evaluate the value of nomogram in predicting prognosis. Results: The overall survival of GC in the IL-6 HIGH and IL-6 LOW groups were 47.8 months (95% CI: 42.1-53.4) and 57.9 months (95% CI: 54.1-61.7), respectively, with significant differences (p = 0.0046). Average tumor size of GC (p = 0.000) and nerve invasion (p = 0.018) were statistically significant between two groups. Multivariate analysis revealed that the factors affecting prognosis were IL-6 (<5.51 and ⩾5.51 pg/ml) (Hazard Ratio(HR): 1.665, 95% CI: 1.026-2.703, p = 0.039), N stage (HR: 1.336, 95% CI: 1.106-1.615, p = 0.003), and T stage (HR: 1.268, 95% CI: 0.998-1.611, p = 0.052), which were included in the nomogram with a C-index of 0.71. The current data calculated TNM staging C-index was 0.68, and the p-value for the difference between the two models was 0.08. Internal validation revealed that the predicted overall survival did not differ significantly from the actual observed patient survival. Conclusion: The differential expression of IL-6 has a tendency to differentiate the prognosis of GC patients. IL-6, N stage, and T stage are independent prognostic factors, and the new survival prognostic model consisting of the above three indicators is better than the classical TNM staging system. Trial registration: This study is a retrospective study, which does not require clinical registration.

4.
Ther Adv Med Oncol ; 15: 17588359231183678, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435560

RESUMO

Background: Research on the correlation between circulating tumor cells (CTCs) and gastric cancer (GC) has increased rapidly in recent years. However, whether CTCs are associated with GC patient prognosis is highly controversial. Objective: This study aims to evaluate the value of CTCs to predict the prognosis of GC patients. Design: A meta-analysis. Data Sources and Methods: We searched the PubMed, Embase, and Cochrane Library databases for studies that reported the prognostic value of CTCs in GC patients before October 2022. The association between CTCs and overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS) and progression-free survival (PFS) of GC patients was assessed. Subgroup analyses were stratified by sampling times (pre-treatment and post-treatment), detection targets, detection method, treatment method, tumor stage, region, and HR (Hazard Ratio) extraction methods. Sensitivity analysis was performed by removing individual studies to assess the stability of the results. Publication bias was evaluated using funnel plots, Egger's test, and Begg's test. Results: We initially screened 2000 studies, of which 28 were available for further analysis, involving 2383 GC patients. The pooled analysis concluded that the detection of CTCs was associated with poor OS (HR = 1.933, 95% CI 1.657-2.256, p < 0.001), DFS/RFS (HR = 3.228, 95% CI 2.475-4.211, p < 0.001), and PFS (HR = 3.272, 95% CI 1.970-5.435, p < 0.001). Furthermore, the subgroup analysis stratified by tumor stage (p < 0.01), HR extraction methods (p < 0.001), detection targets (p < 0.001), detection method (p < 0.001), sampling times (p < 0.001), and treatment method (p < 0.001) all showed that CTC detection was associated with poor OS and DFS/RFS for GC patients. Furthermore, the study showed that CTCs were associated with the poor DFS/RFS of GC when CTCs were detected for patients from Asian or No-Asian regions (p < 0.05). In addition, higher CTCs predicted poorer OS for GC patients who are from Asian regions (p < 0.001), but without statistical difference for GC patients from No-Asian regions (p = 0.490). Conclusion: CTC detection in peripheral blood was associated with poor OS, DFS/RFS, and PFS in patients with GC.

5.
J Invest Surg ; 36(1): 2150337, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36451615

RESUMO

Background: Patients with gastrointestinal cancer often suffer from malnutrition during tumor progression. Malnutrition is associated with postoperative complications and decreased quality of life. Supporting cancer patients with proper nutrition is vital for improving their prognoses.Method: Google scholar and PubMed database searches were performed. Selection criteria included gastrointestinal cancer, surgery, ω - 3 fatty acids, randomized clinical trials from 2007 to August 2022.Conclusion: Nutritional therapy includes nutritional counseling, enteral nutrition, parenteral nutrition, and oral nutritional supplements. Immune nutrients like glutamine and ω-3 fatty acid have been demonstrated with benefits in reducing inflammatory responses and postoperative complications, regulating immune function and improving prognosis.


Assuntos
Neoplasias Gastrointestinais , Desnutrição , Humanos , Qualidade de Vida , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/cirurgia , Desnutrição/etiologia , Desnutrição/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Bases de Dados Factuais
6.
Surgery ; 173(2): 375-382, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36379744

RESUMO

BACKGROUND: Vagus nerve-preserving gastrectomy is increasingly popular in treating gastric cancer in the early stage, however the long and short-term outcomes after gastrectomy while preserving the celiac branch of the vagus nerve are not well defined. We aimed to summarize and compare perioperative and longer-term outcomes after celiac branch vagus nerve-preserving gastrectomy (CBP, preserving both the celiac and hepatic branches of the vagus nerve), compared to those without CBP (non-CBP, only the hepatic branch of the vagus nerve is preserved). METHODS: We searched the Embase, PubMed, Cochrane Library and Web of Science databases for papers published before October 2021. The primary results were evaluated by short-term and long-term postoperative complications, whereas the secondary outcomes included surgery-related parameters, recovery-related parameters and overall survival. Random-effects or fixed-effects model were used to estimate odds ratio, and weighted mean difference for the outcomes. The underlying publication bias was identified via funnel charts, Begg's test and Egger's test. Sensitivity analysis was conducted by removing the research one by one. RESULTS: A total of 9 studies consisting of 8 retrospective studies and one randomized control trial were included. The analysis included 1,109 patients, with 568 (51.2%) of patients receiving CBP and 541 (48.8%) patients who received non-CBP. The CBP group had a shorter time in terms of first flatus (weighted mean difference = -0.436, 95% confidence interval: -0.603 to -0.269; P < 0.001) and hospital stay (weighted mean difference = -0.456, 95% confidence interval: -0.874 to -0.037, P = 0.033) than the non-CBP group, but the time to the start of oral intake was comparable between the groups. Regarding short-term complications and surgery-related parameters, between CBP and non-CBP, no evident differences were observed in pancreatic complications, anastomotic leakage, postoperative bleeding, operation time, blood loss or lymph nodes examined. In terms of long-term complications, the incidence of gallstones in CBP was lower than that in non-CBP (odds ratio = 0.582, 95% confidence interval: 0.356-0.953, P = 0.031), and the incidence of bile reflux in CBP was lower than that in non-CBP (odds ratio = 0.473, 95% confidence interval: 0.280-0.800, P = 0.005). However, the prevalence rates of diarrhea, early dumping syndrome, esophageal reflux, and delayed gastric emptying were comparable between CBP and non-CBP. CONCLUSION: The present research showed that gastric cancer patients in the early stage under CBP were superior to those without CBP in terms of incidence of gallstones, bile reflux, time of first flatus and hospital stay. Furthermore, it is imperative to conduct randomized control studies with larger sample sizes to determine the oncological survival outcomes when preserving the celiac branch.


Assuntos
Refluxo Biliar , Cálculos Biliares , Laparoscopia , Neoplasias Gástricas , Humanos , Refluxo Biliar/complicações , Refluxo Biliar/cirurgia , Flatulência/complicações , Flatulência/cirurgia , Cálculos Biliares/cirurgia , Gastrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Nervo Vago/cirurgia
7.
Cancer Res ; 82(13): 2431-2443, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35544764

RESUMO

Micropeptides are a recently discovered class of molecules that play vital roles in various cellular processes, including differentiation, proliferation, and apoptosis. Here, we sought to identify cancer-associated micropeptides and to uncover their mechanistic functions. A micropeptide named short transmembrane protein 1 (STMP1) that localizes at the inner mitochondrial membrane was identified to be upregulated in various cancer types and associated with metastasis and recurrence of hepatocellular carcinoma. Both gain- and loss-of-function studies revealed that STMP1 increased dynamin-related protein 1 (DRP1) activation to promote mitochondrial fission and enhanced migration of tumor cells. STMP1 silencing inhibited in vivo tumor metastasis in xenograft mouse models. Overexpression of STMP1 led to redistribution of mitochondria to the leading edge of cells and enhanced lamellipodia formation. Treatment with a DRP1 inhibitor abrogated the promotive effect of STMP1 on mitochondrial fission, lamellipodia formation, and tumor cell migration in vitro and metastasis in vivo. Furthermore, STMP1 interacted with myosin heavy chain 9 (MYH9), the subunit of nonmuscle myosin II, and silencing MYH9 abrogated STMP1-induced DRP1 activation, mitochondrial fission, and cell migration. Collectively, this study identifies STMP1 as a critical regulator of metastasis and a novel unit of the mitochondrial fission protein machinery, providing a potential therapeutic target for treating metastases. SIGNIFICANCE: This study identifies the mitochondrial micropeptide STMP1 as a regulator of metastasis that promotes mitochondrial fission and tumor cell migration via DRP1 and MYH9.


Assuntos
Neoplasias Hepáticas , Proteínas de Membrana , Dinâmica Mitocondrial , Proteínas Mitocondriais , Animais , Apoptose , Dinaminas/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo
8.
Nutrients ; 14(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35406085

RESUMO

BACKGROUND: Early enteral nutrition (EN) after abdominal surgery can improve the prognosis of patients. However, the high feeding intolerance (FI) rate is the primary factor impeding postoperative EN. METHODS: Sixty-seven patients who underwent radical subtotal or total gastrectomy for gastric cancer (GC) were randomly allocated to the preoperative oral nutritional supplement group (ONS group) or dietary advice alone (DA group). Both groups were fed via nasojejunal tubes (NJs) from the first day after surgery to the fifth day. The primary endpoint is the FI rate. RESULTS: Of the patients, 66 completed the trial (31 in the ONS group, 35 in the DA group). The FI rate in the ONS group was lower than that in the DA group (25.8% vs. 31.4%, p = 0.249). The postoperative five-day 50% energy compliance rate in the ONS group was higher than that in the DA group (54.8% vs. 48.6%, p = 0.465). The main gastrointestinal intolerance symptoms were distension (ONS vs. DA: 45.2% vs. 62.9, p = 0.150) and abdominal pain (ONS vs. DA: 29.0% vs. 45.7%, p = 0.226). Postoperative nausea/vomiting rate and heartburn/reflux rate were similar between the two groups. We noted no difference in perioperative serum indices, short-term prognosis or postoperative complication rates between the two groups. CONCLUSIONS: The study shows that short-term preoperative ONS cannot significantly improve FI and the energy compliance rate in the early stage after radical gastrectomy.


Assuntos
Nutrição Enteral , Neoplasias Gástricas , Humanos , Recém-Nascido , Prognóstico , Estudos Prospectivos , Método Simples-Cego , Neoplasias Gástricas/cirurgia
9.
Int J Nanomedicine ; 16: 3581-3598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079251

RESUMO

BACKGROUND: BF211, a derivative of bufalin (BF), shows significantly improved solubility and potent antitumor efficiency compared to BF. Unfortunately, the unwanted toxicity such as cardiotoxicity caused by unspecific distribution has hindered its clinical use. METHODS: PEGylated BF211 liposomes (BF211@Lipo) were designed and optimizely prepared based on the pre-prescription research. In vitro and in vivo cardiotoxicity was evaluated. In vivo pharmacokinetics and biodistribution of BF211@Lipo were investigated. In vivo antitumor activity and toxicity were evaluated in HepG2 cell xenograft models. The rapid-release triggered by Poloxamer 188 (P188) was assessed in vitro and in vivo. RESULTS: The optimized BF211@Lipo displayed a spherical morphology with a size of (164.6 ± 10.3) nm and a high encapsulation efficiency of (93.24 ± 2.15) %. The in vivo concentration-time curves of BF211 loaded in liposomes showed a prolonged half-life in plasma and increased tumor accumulation. No obvious abnormality in electrocardiograms was observed in guinea pigs even at 9 mg/kg. Moreover, to improve the efficient release of BF211@Lipo, a surfactant-assisted rapid-release strategy was developed, and the release-promoting mechanism was revealed by the fluorescence resonance energy transfer (FRET) and fluorescence nanoparticle tracking analysis (fl-NTA) technology. Sequential injection of BF211@Lipo and P188 could ignite the "cold" liposomes locally in tumor regions, facilitating the burst release of BF211 and enhancing the therapeutic index. CONCLUSION: Our progressive efforts that begin with preparation technology and dosage regimen enable BF211 to like a drug, providing a promising nano platform to deliver the cardiac glycosides and alleviate the side effects by decreasing unspecific biodistribution.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Bufanolídeos/administração & dosagem , Bufanolídeos/farmacologia , Coração/efeitos dos fármacos , Tensoativos/química , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Bufanolídeos/química , Bufanolídeos/toxicidade , Cobaias , Células Hep G2 , Humanos , Lipossomos , Nanopartículas/química , Poloxâmero/química , Solubilidade , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Int J Nanomedicine ; 16: 1575-1586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664572

RESUMO

BACKGROUND: Exosomes are a type of membrane vesicles secreted by living cells. Recent studies suggest exosome-like nanovesicles (ELNVs) from fruits and vegetables are involved in tissue renewal process and functional regulation against inflammatory diseases or cancers. However, there are few reports on ELNVs derived from medicinal plants. METHODS: ELNVs derived from Asparagus cochinchinensis (Lour.) Merr. (ACNVs) were isolated and characterized. Cytotoxicity, antiproliferative and apoptosis-inducing capacity of ACNVs against hepatoma carcinoma cell were assessed. The endocytosis mechanism of ACNVs was evaluated on Hep G2 cells in the presence of different endocytosis inhibitors. In vivo distribution of ACNVs was detected in healthy and tumor-bearing mice after scavenger receptors (SRs) blockade. PEG engineering of ACNVs was achieved through optimizing the pharmacokinetic profiles. In vivo antitumor activity and toxicity were evaluated in Hep G2 cell xenograft model. RESULTS: ACNVs were isolated and purified using a differential centrifugation method accompanied by sucrose gradient ultracentrifugation. The optimized ACNVs had an average size of about 119 nm and showed a typical cup-shaped nanostructure containing lipids, proteins, and RNAs. ACNVs were found to possess specific antitumor cell proliferation activity associated with an apoptosis-inducing pathway. ACNVs could be internalized into tumor cells mainly via phagocytosis, but they were quickly cleared once entering the blood. Blocking the SRs or PEGylation decoration prolonged the blood circulation time and increased the accumulation of ACNVs in tumor sites. In vivo antitumor results showed that PEGylated ACNVs could significantly inhibit tumor growth without side effects. CONCLUSION: This study provides a promising functional nano platform derived from edible Asparagus cochinchinensis that can be used in antitumor therapy with negligible side effects.


Assuntos
Asparagaceae/química , Carcinoma Hepatocelular/patologia , Exossomos/metabolismo , Neoplasias Hepáticas/patologia , Nanopartículas/química , Nanotecnologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/efeitos adversos , Nanopartículas/ultraestrutura , Polietilenoglicóis/química , Distribuição Tecidual/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Eur J Med Chem ; 192: 112189, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151834

RESUMO

Based on fragment-based virtual screening and bioisoterism strategies, novel indazole and pyrazolo[3,4-b] pyridine derivatives as HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDACs, especially compounds 15k and 15m were identified as potent inhibitors of HDAC1 (IC50 = 2.7 nM and IC50 = 3.1 nM), HDAC2 (IC50 = 4.2 nM and IC50 = 3.6 nM) and HDAC8 (IC50 = 3.6 nM and IC50 = 3.3 nM). Further anti-proliferation assays revealed that compounds 15k and 15m showed better anti-proliferative activities against HCT-116 and HeLa cells than positive control SAHA. The western blot analysis results indicated that compounds 15k and 15m noticeably up-regulated the level of acetylated α-tubulin and histone H3. In addition, the two compounds 15k and 15m could arrest cell cycle in G2/M phase and promote cell apoptosis, which was similar as the reference compound SAHA. Through the molecular docking and dynamic studies, the potent HDAC inhibitory activities mainly caused by van der Waals and electrostatic interactions with the HDACs.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Histona Desacetilases/farmacologia , Indazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Células HeLa , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/antagonistas & inibidores , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Indazóis/síntese química , Indazóis/química , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Relação Estrutura-Atividade
12.
J Enzyme Inhib Med Chem ; 35(1): 72-84, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31682465

RESUMO

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.


Assuntos
Antineoplásicos/farmacologia , Benzotiazóis/farmacologia , Desenho de Fármacos , Indazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzotiazóis/síntese química , Benzotiazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indazóis/síntese química , Indazóis/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
13.
World J Clin Cases ; 7(23): 4137-4143, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832419

RESUMO

BACKGROUND: Gastric cancer is the third most lethal malignant tumor worldwide. Metastasis has always been a major cause of poor prognosis. Epidemiological evidence shows that the most common sites for metastasis of gastric carcinoma are the liver (48%), peritoneum (32%), lung (15%), and bone (12%); however, subcutaneous metastasis is are and occurs in approximately 0.8% of cases. We report a rare case of armpit subcutaneous metastasis of gastric cancer. The best surgical window was missed, as a result of lacking attention of the mass. CASE SUMMARY: A 69-year-old man who had previously undergone radical gastrectomy and received eight cycles of oral chemotherapy for gastric cancer showed a rapidly growing mass in his the left armpit; within just 3 mo, the mass grew to a size of 6.9 cm × 4.4 cm × 5.7 cm. Color Doppler ultrasonography and Positron emission tomography/computed tomography prompted the possibility of metastasis of the malignancy. Fine needle aspiration biopsy guided by color Doppler ultrasound showed the presence of cancer cells in the mass. Immunohistochemical examination showed CDX-2 (+), PCK (+), CK20 (+), CK7 (-), and TTF (-), which supported the metastasis of gastric cancer. Considering the risk of resection, the patient did not undergo surgical treatment. CONCLUSION: The case indicates that unidentified subcutaneous masses in patients with a history of gastric cancer should be carefully evaluated.

14.
BMC Public Health ; 19(1): 1141, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429727

RESUMO

BACKGROUND: The consumption of non-carbonated sugar-sweetened beverages (NCSSBs) has many adverse health effects. However, the sugar and energy content in NCSSBs sold in China remain unknown. We aimed to investigate the sugar and energy content of NCSSBs in China and how these contents were labelled. METHODS: A cross-sectional survey was conducted in 15 supermarkets in Haidian District, Beijing from July to October 2017. The product packaging and nutrient information panels of NCSSBs were recorded to obtain type of products (local/imported), serving size, nutrient contents of carbohydrate, sugar and energy. For those NCSSBs without sugar content information, we used carbohydrate content as a replacement. RESULTS: A total of 463 NCSSBs met the inclusion criteria and were included in our analysis. The median of sugar content and energy content was 9.6 [interquartile range (IQR): 7.1-11.3] g/100 ml and 176 (IQR: 121-201) kJ/100 ml. The median of sugar contents in juice drinks, tea-based beverages, sports drinks and energy drinks were 10.4, 8.5, 5.0 and 7.4 g/100 ml. Imported products had higher sugar and energy content than local products. There were 95.2% products of NCSSBs receiving a 'red'(high) label for sugars per portion according to the UK criteria, and 81.6% products exceeding the daily free sugar intake recommendation from the World Health Organization (25 g). There were 82 (17.7%) products with sugar content on the nutrition labels and 60.2% of them were imported products. CONCLUSIONS: NCSSBs had high sugar and energy content, and few of them provided sugar content information on their nutrition labels especially in local products. Measures including developing better regulation of labelling, reducing sugar content and restricting the serving size are needed for reducing sugar intakes in China.


Assuntos
Bebidas/análise , Sacarose Alimentar/análise , Edulcorantes/análise , Pequim , Bebidas/provisão & distribuição , Estudos Transversais , Bebidas Energéticas/análise , Ingestão de Energia , Rotulagem de Alimentos/estatística & dados numéricos , Humanos , Recomendações Nutricionais
15.
Zhongguo Zhong Yao Za Zhi ; 41(1): 75-82, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28845644

RESUMO

To optimize the one-step pelletization technology of Fuke IV (FKIV) granules by response surface methodology. With the qualified rate of granules as evaluation indexes, 6 factors affecting one-step pelletization technology were investigated, significant levels of each factor were evaluated and the primal influential factors were determined by Plackett-Burman experimental design. According to the Plackett-Burman experimental design, the qualified rates of granules, moisture capacity and angle of repose as the evaluation indexes, Box-Behnken design with three levels and three factors was established for quadratic regression fitting of the models. Then the experimental results were optimized by Response Optimizer. The best process conditions were determined as follows: the extract relative density of 1.20, inlet air temperature of 88 ℃, and atomization pressure of 0.28 MPa. FKIV granules were prepared by the optimized experimental scheme. The determined qualified rate, moisture capacity and angle of response were 93.65%, 3.76% and 23.19° respectively for the granules, basically similar to the predicted values, indicating that the optimal process conditions were in line with the manufacturing requirements.


Assuntos
Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Composição de Medicamentos/instrumentação , Projetos de Pesquisa , Temperatura
16.
Nat Prod Res ; 29(23): 2197-202, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25966868

RESUMO

Strain HSY05 was isolated from sea sediment collected from the South China Sea and was later identified as Penicillium oxalicum by 16S rDNA sequence analysis. Various chromatographic processes led to the isolation and purification of two metabolites from the fermentation culture of HSY05, including one new compound, 2,2',4,4'-tetrahyoxy-8'-methyl-6-methoxy-acyl-ethyl-diphenylmethanone (1), and a known compound secalonic acid D (SAD, 2), as characterised by UV, IR, 1D, 2D-NMR and MS data. The inhibitory activities against topoisomerase I of these two compounds were evaluated. The result showed that in addition to the known topo I inhibitor SAD (2), compound 1 also exhibited a moderate inhibitory effect.


Assuntos
Penicillium/química , Inibidores da Topoisomerase I/química , Benzofenonas/química , Benzofenonas/isolamento & purificação , China , Sedimentos Geológicos/microbiologia , Estrutura Molecular , Oceanos e Mares , Penicillium/isolamento & purificação , Inibidores da Topoisomerase I/isolamento & purificação , Xantonas/química , Xantonas/isolamento & purificação
17.
Zhonghua Yi Xue Za Zhi ; 85(10): 667-70, 2005 Mar 16.
Artigo em Chinês | MEDLINE | ID: mdl-15932728

RESUMO

OBJECTIVE: To study the pathological characteristics of thyroid gland and the changes on hormone content of thyroid cells in severe acute respiratory syndrome (SARS) patients. METHOD: Hematoxylin and eosin staining and light microscopy were used to examine the histology of the thyroid tissues from 4 dead SARS patients and 5 healthy thyroid samples used as negative controls. Immunohistochemistry was used, with monoclonal antibodies, to detect the thyroglobulin (TG), calcitonin and parathyroid hormone (PTH) in the thyroid glands. RESULTS: Deformation, enlargement, and dystrophy of follicular cells in thyroid glands were found in the SARS patients. The normal follicular epithelial cells were strongly TG positive, however, the number and intensity of TG positive follicular epithelial cells were significantly lower in the SARS patients. Calcitonin positive cells were found in the normal thyroid glands and not in the thyroid glands of the SARS patients. PTH positive cells were seen in the normal thyroid glands and those of the SARS patients with a slightly weaker intensity of reaction, however, with significant difference in IOD (P < 0.01) and without significant difference in mean slight absorption MOD (P > 0.05). CONCLUSION: The thyroid tissue structure and morphology in SARS patients were significantly changed, involving both follicular epithelial cells and parafollicular cells; which may imply that the hormonal production of follicular epithelial cells and the parafollicular cells were affected.


Assuntos
Calcitonina/análise , Síndrome Respiratória Aguda Grave/patologia , Tireoglobulina/análise , Glândula Tireoide/patologia , Adulto , Cadáver , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/análise
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