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1.
BMC Cancer ; 23(1): 958, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817078

RESUMO

BACKGROUND: There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC. METHODS: Patients with mPDAC who received the combination of trametinib and HCQ or CDK4/6 inhibitors as third- or later-line therapy were reviewed. The efficacy and prognosis were further analyzed. RESULTS: A total of 13 mPDAC patients were enrolled, of whom 8 and 5 patients were treated with trametinib plus HCQ or a CDK4/6 inhibitor (palbociclib or abemaciclib), respectively. All enrolled patients had either KRAS G12D or G12V mutations and had received a median of 3 prior lines of therapy (range, 2-6). The median trametinib treatment duration was 1.4 months. Of the 10 patients with measurable disease, only 1 patient achieved stable disease, and the remaining patients had progressive disease. Moreover, in patients treated with trametinib plus HCQ and a CDK4/6 inhibitor, the median progression-free survival was 2.0 and 2.8 months, respectively, and the median overall survival was 4.2 and 4.7 months, respectively. Moreover, 5 (50%) patients experienced grade 3-4 adverse events in 10 patients with available safety data. CONCLUSIONS: The combination of trametinib and HCQ or CDK4/6 inhibitors may not be an effective later-line treatment for mPDAC, and the current preliminary findings need to be confirmed by other studies with larger sample sizes.


Assuntos
Adenocarcinoma , Antineoplásicos , Hidroxicloroquina , Neoplasias Pancreáticas , Inibidores de Proteínas Quinases , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quimioterapia Combinada , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Pancreáticas
2.
J Cancer Surviv ; 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37460857

RESUMO

BACKGROUND: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) need timely medical assistance since the emergence of complications due to the disease and antitumor treatment. Studies have confirmed that instant messaging can improve the quality of life and compliance of cancer patients. However, the prognostic role of instant doctor-patient communication based on instant messaging applications in PDAC has not been studied. METHODS: Patients with PDAC who received first-line chemotherapy at Peking Union Medical College Hospital between January 2015 and October 2022 were reviewed. We categorized patients into two groups according to whether they received WeChat-based instant doctor-patient communication, and the prognosis and toxicity data between the two groups were compared. RESULTS: A total of 431 PDAC patients were enrolled, of whom 163 had long-term instant communication with their doctors based on WeChat, and 268 did not receive WeChat-based instant communication. There was no significant correlation between WeChat-based communication and first-line chemotherapy overall response rate (14.1% vs. 8.6%, p = 0.074), incidence of grade ≥ 3 adverse events (66.9% vs. 65.7%, p = 0.814) or overall survival (14.7 vs. 13.9 months, p = 0.170) in all enrolled patients. However, patients who received WeChat-based instant communication had a higher completion rate of first-line chemotherapy (42.0% vs. 30.7%, p = 0.023). Consistently, in the patients who developed grade ≥ 3 adverse events (n = 231), those who received WeChat-based instant communication had significantly longer overall survival (17.3 vs. 15.3 months, p = 0.018), even after adjustment for biases. CONCLUSIONS: WeChat-based instant doctor-patient communication demonstrated no superiority in improving the efficacy of chemotherapy or preventing chemotherapy toxicity in PDAC patients, but it may contribute to improving the completion rate of chemotherapy and the prognosis in patients who experienced severe adverse events. IMPLICATIONS FOR CANCER SURVIVORS: Instant doctor‒patient communication may help to timely and appropriately deal with adverse events and prolong the survival time of patients with PDAC, supporting the promotion of mobile technology in clinical practice.

3.
Front Oncol ; 13: 1195848, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346066

RESUMO

Objective: The prognosis of patients with advanced cancers of the upper gastrointestinal (UGI) tract is poor. Systemic chemotherapy forms the basis for their treatment, with limited efficacy. Biomarkers have been introduced into clinical practice for cancer management. This study aimed to investigate the predictive and prognostic values of circulating biomarkers in patients with advanced esophageal and gastric cancers receiving chemotherapy. Design: Overall, 92 patients with advanced esophageal squamous cell carcinoma (ESCC; n = 38) and gastric adenocarcinoma (GAC; n = 54) were enrolled. We analyzed the association of circulating lymphocyte subsets, inflammatory markers, and blood cell counts with treatment efficacy and patient survival. Results: Significant differences were identified in peripheral blood parameters between the groups with different clinicopathological features. Hemoglobin (Hb, p = 0.014), eosinophil counts (p = 0.028), CD4+CD28+T/CD4+T percentage (p = 0.049), CD8+CD38+T/CD8+T percentage (p = 0.044), memory CD4+T (p = 0.007), and CD4+CD28+T (p = 0.007) were determined as predictors for achieving non-PD (progression disease) in the ESCC cohort. High levels of eosinophils (p = 0.030) and memory CD4+T cells (p = 0.026) and high eosinophil-to-lymphocyte ratio (ELR, p = 0.013) were predictors of non-PD in patients with GAC. The combined detection models exhibited good ability to distinguish between partial response (PR)/non-PR and PD/non-PD in patients with ESCC and GAC, respectively. Using the multivariate Cox model, the Eastern Cooperative Oncology Group (ECOG) score status (hazard ratio [HR]: 4.818, 95% confidence intervals [CI]: 2.076-11.184, p < 0.001) and eosinophil count (HR: 0.276, 95% CI: 0.120-0.636, p = 0.003) were independent prognostic factors of progression-free survival (PFS) in patients with ESCC. Metastatic sites (HR: 2.092, 95% CI: 1.307-3.351, p = 0.002) and eosinophil-to-lymphocyte ratio (ELR; HR: 0.379, 95% CI: 0.161-0.893, p = 0.027) were independent prognostic factors for overall survival (OS) in patients with ESCC. Differentiation (HR: 0.041, 95% CI: 0.200-0.803, p = 0.010), memory CD4+T (HR: 0.304, 95% CI: 0.137-0.675, p = 0.003), NK cells (HR: 2.302, 95% CI: 1.044-3.953, p = 0.037), and C-reactive protein-to-lymphocyte ratio (CLR; HR: 2.070, 95% CI: 1.024-4.186, p = 0.043) were independent prognostic factors for PFS in patients with GAC. Total lymphocyte counts (HR: 0.260, 95% CI: 0.086-0.783, p = 0.017), CD8+T (HR: 0.405, 95% CI: 0.165-0.997, p = 0.049), NK cells (HR: 3.395, 95% CI: 1.592-7.238, p = 0.002), and monocyte-to-lymphocyte ratio (MLR; HR: 3.076, 95% CI: 1.488-6.360, p = 0.002) were identified as independent prognostic factors associated with OS of GAC. Conclusion: Lymphocyte subsets, blood cell counts, and inflammatory parameters may predict the chemotherapeutic response and prognosis in ESCC and GAC. A combination of these markers can be used to stratify patients into risk groups, which could improve treatment strategies.

4.
Front Immunol ; 14: 1125876, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969245

RESUMO

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes. Methods: We retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry. Results: Patients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/µL, p < 0.001). Using 190/µL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/µL. Conclusions: High circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/µL) may also indicate the emergence of severe irAEs.


Assuntos
Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Antígenos CD28/metabolismo , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos
5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 899-905, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36325789

RESUMO

Gastric cancer ranks as the fifth most common malignant tumor worldwide and the fourth leading cause of cancer-related deaths.Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a special type of gastric adenocarcinoma,the prognosis of which can be improved by trastuzumab plus cytotoxic chemotherapy such as cisplatin and fluorouracil.Pembrolizumab on the basis of Tmabplus chemotherapy can further improve the overall response rate,which has become the first-line standardized therapy against HER2-positive gastric cancer.However,there are still some obstacles such as the innate resistance to Tmab in specific populations.The research on HER2-targeted therapy provides clues for clinical decision-making.This review documents the current neoadjuvant and adjuvant therapies against late-stage HER2-positive gastric cancer,as well as the progress in novel HER2 pathway-targeted drugs.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2 , Trastuzumab/uso terapêutico
6.
Artigo em Inglês | IBECS | ID: ibc-203812

RESUMO

BackgroundThe incidence and mortality of gastrointestinal (GI) tumors are high in China. Some studies suggest that the gut microbiota is related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in healthy control participants and patients with esophageal cancer, gastric cancer, and colorectal cancer.MethodsPatients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction.ResultsSignificant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients (n = 130) and healthy controls (n = 147). The abundance of Faecalibacterium prausnitzii, Clostridium clostridioforme and Bifidobacterium adolescent in tumor groups were all significantly lower than in the control group (P < 0.05). The levels of Blautia producta and R. faecis in the gastric (n = 46) and colorectal cancer (n = 44) groups were significantly lower than those in the control group (P < 0.05). The level of Butyricicoccus pullicaecorum in the esophageal cancer (n = 40) and gastric cancer groups was significantly lower than that in the control group (P < 0.05).


Assuntos
Humanos , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Estudos de Casos e Controles , Metabolômica , RNA Ribossômico 16S
7.
Clin Transl Oncol ; 24(6): 1134-1147, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35167015

RESUMO

BACKGROUND: The incidence and mortality of gastrointestinal (GI) tumors are high in China. Some studies suggest that the gut microbiota is related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in healthy control participants and patients with esophageal cancer, gastric cancer, and colorectal cancer. METHODS: Patients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction. RESULTS: Significant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients (n = 130) and healthy controls (n = 147). The abundance of Faecalibacterium prausnitzii, Clostridium clostridioforme and Bifidobacterium adolescent in tumor groups were all significantly lower than in the control group (P < 0.05). The levels of Blautia producta and R. faecis in the gastric (n = 46) and colorectal cancer (n = 44) groups were significantly lower than those in the control group (P < 0.05). The level of Butyricicoccus pullicaecorum in the esophageal cancer (n = 40) and gastric cancer groups was significantly lower than that in the control group (P < 0.05). B. fragilis, Akkermansia muciniphila, Clostridium hathewayi and Alistipes finegoldii were overabundant in the different tumor groups compared with the control (P < 0.05). We observed significant differences in functional metabolism and cell biological function between the tumor and control groups (P < 0.05). Optimal microbial markers were identified on a random forest model and achieved an area under the curve of 85.59% between 130 GI cancer samples and 147 control samples. The respective AUC values were 86.89%, 97.11%, and 79.1% in detecting esophageal cancer, gastric cancer, and colorectal cancer. CONCLUSIONS: Patients with esophageal or gastric cancers had similar features of fecal bacteria as those with colorectal cancer. The metabolic function of fecal bacteria in the gastrointestinal cancer patients and the healthy controls were different. The microbial signatures may potentially be applied to distinguish GI cancer patients from healthy people as a non-invasive diagnostic biomarker.


Assuntos
Neoplasias Colorretais , Neoplasias Esofágicas , Microbiota , Neoplasias Gástricas , Adolescente , Bactérias , Humanos , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo
8.
BMC Pulm Med ; 21(1): 282, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488711

RESUMO

BACKGROUND: Treatment for non-small cell lung cancer (NSCLC) has greatly improved in recent years. However, noninvasive early screening for carcinogenesis and progression unclear. The aim of this study was to explore the predictive value of peripheral blood immune cells in untreated NSCLC patients. METHODS: We retrospectively enrolled 305 untreated NSCLC patients and 132 healthy participants from February 2016 to August 2019 in Peking Union Medical College Hospital. Immune cell levels were determined by flow cytometry and routine blood tests. RESULTS: NSCLC patients had lower levels of T lymphocytes, NK cells, CD8+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells and higher levels of CD4+ T cells, memory CD4+/CD4+ T cells, memory CD4+ T cells, CD4+CD28+/CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+/CD8+ T cells, CD8+HLA-DR+/CD8+ T cells, CD8+HLA-DR+ T cells T cells, CD8+CD38+/CD8+ T cells, CD8+CD38+ T cells and CD4+/CD8+ T cells than those in controls. The percentages of specific lymphocyte subtypes were significantly different in cancer patients versus healthy individuals. For instance, cancer patients had lower levels of B cells, CD4+ T cells, naïve CD4+/CD4+ T cells, naïve CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+ T cells and higher levels of NK cells, white blood cells (WBC), monocytes, neutrophils, eosinophils, basophils, monocytes to lymphocyte ratio (MLR), neutrophils to lymphocyte ratio (NLR), eosinophil to lymphocyte ratio (ELR), basophil to lymphocyte ratio (BLR), and blood platelet to lymphocyte ratio (PLR). CONCLUSIONS: Abnormal T cell levels can be used as an independent predictive biomarker for noninvasive early screening in NSCLC occurrence and progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Linfócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microambiente Tumoral
9.
Front Oncol ; 11: 781697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004303

RESUMO

OBJECTIVE: The prognosis of advanced gastrointestinal cancer is poor. There are studies indicating that gut microbes might have the predictive ability to evaluate the outcome of cancer therapy, especially immunotherapy. There is limited evidence to date on the influence of microbes on chemotherapeutic response. DESIGN: In total, 130 patients with advanced or metastatic esophageal (n=40), gastric (n=46), and colorectal cancer (n=44) were enrolled. We included 147 healthy people as controls and used 16S rRNA sequencing to analyze the fecal microbiota. RESULTS: Significant differences in the abundance of fecal microbiota between patients with gastrointestinal cancer and controls were identified. The abundance of Bacteroides fragilis, Escherichia coli, Akkermansia muciniphila, Clostridium hathewayi, and Alistipes finegoldii were significantly increased in the patient group. Faecalibacterium prausnitzii, Roseburia faecis, Clostridium clostridioforme, Blautia producta, Bifidobacterium adolescent, and Butyricicoccus pullicaecorum taxa were significantly more abundant in the controls. The amount of R. faecis in non-responders (NR) was more likely to decrease significantly after chemotherapy, while the amount mostly increased in responders (R) (P=0.040). The optimal abundance variation of R. faecis may be a predictor for distinguishing patients with PD from those with non-PD in all patients with gastrointestinal cancer, with a sensitivity of 75.0% and a specificity of 93.9%. CONCLUSION: The gut microbiome of patients with esophageal cancer, gastric cancer, and colorectal cancer differs from those of healthy people. The abundance alteration of R. faecis in patients with GI cancer might be a predictor of chemotherapy efficacy.

10.
J Int Med Res ; 48(8): 300060520939672, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32865090

RESUMO

OBJECTIVE: We investigated physical deviation and precocious puberty among school-aged children in Leshan City, to provide a theoretical basis for the management of precocious puberty in children. METHODS: We selected 12 primary schools of Leshan City using a cluster random sampling method and conducted physical examinations among healthy students aged 4 12 years. A total of 11,000 students were recruited (5502 boys and 5498 girls). We measured body mass index (BMI), and participants were tested for precocious puberty according to the Tanner stages and standard maps. Nutritional status was also evaluated. RESULTS: Obese and overweight children accounted for a high proportion of participants; the prevalence of underweight was the lowest. The prevalence of obesity among boys was higher than that in girls. Precocious puberty was mainly observed in girls, particularly those age 7 years old. The prevalence of precocious puberty among overweight and obese children was higher than that in children with normal weight. CONCLUSION: We identified a significant sex difference in precocious puberty among children in Leshan City. Overweight and obesity may be associated with precocious puberty.


Assuntos
Puberdade Precoce , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Sobrepeso/epidemiologia , Prevalência , Puberdade Precoce/epidemiologia , Instituições Acadêmicas
11.
Clin Pharmacol ; 12: 21-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308505

RESUMO

PURPOSE: Trifluridine/tipiracil (FTD/TPI) is approved in Japan, the United States (US), and Europe for metastatic colorectal cancer (mCRC) refractory to standard therapies. This Phase 1b open-label study focused on the pharmacokinetic (PK) and toxicity profiles of FTD/TPI in Chinese patients with solid tumors. METHODS: Patients with definitive histologically or cytologically confirmed advanced/metastatic solid tumors refractory to standard treatments were enrolled. FTD/TPI (35 mg/m2) was administered orally twice daily for five consecutive days, followed by a 2-day recovery. Treatment was repeated for five consecutive days, followed by a 16-day recovery. The primary objective was to assess PK characteristics of FTD, 5-trifluoromethyl-2,4 (1H,3H)-pyrimidinedione (FTY; an inactive form of FTD), and TPI, calculated from plasma concentrations. Additionally, these PK values were compared with those from similar Phase 1 studies in patients from Japan and the US, using Tukey-Kramer's honestly significant difference (HSD) multiple comparison tests. Safety and preliminary efficacy of FTD/TPI were assessed. RESULTS: Fifteen patients (12 males, three females) were enrolled, most with CRC (87%). Geometric mean analysis showed that maximum plasma concentration (Cmax) of FTD increased after multiple administration (from day 1 [3019.5 ng/mL] to day 12 [3693.1 ng/mL]), and the exposure (AUC0-t) increased 2.4-fold (day 1:7796.6 ng/mL•h; day 12:18,181.3 ng/mL•h). There was no meaningful change in the exposure to FTY and TPI throughout the study. HSD tests showed comparable PK for FTD, FTY, and TPI between Chinese and Japanese patients, and comparable exposure to FTD between Chinese and US patients. Eight patients (53.3%) experienced Grade 3 treatment-emergent adverse events, most frequently anemia and fatigue (13.3%, two events each). Median progression-free survival was 1.9 months. CONCLUSION: FTD/TPI had an acceptable safety and efficacy profile and PK characteristics were comparable between Chinese, Japanese, and US patients, suggesting that this treatment may be suitable for Chinese patients with refractory mCRC. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT02261532.

12.
Stem Cells Int ; 2019: 6041816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737076

RESUMO

Human mesenchymal stem cells (hMSCs) are widely used in clinical research because of their multipotential, immunomodulatory, and reparative properties. Previous studies determined that hMSC spheroids from a three-dimensional (3D) culture possess higher therapeutic efficacy than conventional hMSCs from a monolayer (2D) culture. To date, various 3D culture methods have been developed to form hMSC spheroids but most of them used culture medium containing fetal bovine serum (FBS), which is not suitable for further clinical use. Here, we demonstrate that dissociated single MSCs seeded in induced pluripotent stem medium (MiPS) adhere loosely to the dish and spontaneously migrate to form spheroids during day 3 to day 6. Through component deletion screening and complementation experiments, the knockout serum replacement (KSR) was identified as necessary and sufficient for hMSC spheroid formation. Transcriptome analysis showed that the overall expression profiles were highly similar between 2D culture with FBS and KSR-derived spheroids. Interestingly, genes related to inflammatory response, immune response, and angiogenesis were upregulated in spheroids at day 6 and qPCR results further validated the increased expression level of related genes, including STC1, CCL7, HGF, IL24, and TGFB3. When spheroids were replated in normal FBS medium, cells formed a typical spindle-shaped morphology and FACS results showed that the recovered cells retained MSC-specific surface markers, such as CD73, CD90, and CD105. In summary, we developed a practical and convenient method to generate hMSC spheroids for clinical research and therapy.

13.
Oncol Rep ; 40(5): 2710-2721, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30106114

RESUMO

The incidence and mortality of colorectal cancer (CRC) have been rising rapidly in China. A number of miRNAs have been confirmed to be involved in diverse biological processes of CRC. However, whether miR­197 plays a role in migration and invasion of CRC has never been explored. In the present study Transwell chambers were used in in vitro migration and invasion assays. Dual-luciferase reporter assay was employed to confirm the target of miR­197. RT­PCR and IHC staining were performed to quantify miR­197 and IGFBP3 expression, respectively. Clinicopathological features were collected for statistical analysis. We observed that the overexpression of miR­197 significantly promoted migration and invasion in 3 CRC cell lines including HCT8, HCT116 and SW480 (P<0.05), while the inhibition of miR­197 weakened both biological processes (P<0.05). In bioinformatics and dual-luciferase reporter assay, luciferase activities of IGFBP3­WT­transfected cells significantly decreased upon miR­197 overexpression and this inhibitory effect was abolished when miR­197 binding region in IGFBP3 3'­UTR was mutated, which indicated that miR­197 directly suppressed the expression of IGFBP3 in CRC cells by targeting its 3'UTR. Downregulation of the expression of IGFBP3 by using targeted siRNA led to significant enhancement of cell migration and invasion in two CRC cell lines including HCT8 and HCT116 (P<0.05). Finally, in cancerous tissues of CRC patients, the miR­197 level was inversely correlated with the expression of IGFBP3 (P=0.026), which indicated that miR­197 may modulate cell migration and invasion by targeting IGFBP3 in CRC patients. In conclusion, we revealed that miR­197 modulates IGFBP3 and therefore plays a critical role in regulating CRC migration and invasion.


Assuntos
Movimento Celular/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Idoso , Linhagem Celular Tumoral , Estudos de Coortes , Biologia Computacional , Regulação para Baixo , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica/genética , RNA Interferente Pequeno/metabolismo
14.
Biosci Rep ; 37(2)2017 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-28314787

RESUMO

Spermatogenic lineage has been directly generated in spermatogonial stem cell (SSC) conditions from human pluripotent stem cells (PSCs). However, it remains unknown whether mouse embryonic stem cells (ESCs) can directly differentiate into advanced male germ cell lineage in the same conditions. Here, we showed rather low efficiency of germ-like cell generation from mouse ESCs in SSC conditions. Interestingly, addition of retinoic acid (RA) into SSC conditions enabled efficient differentiation of mouse ESCs into germ-like cells, as shown by the activation of spermatogenesis-associated genes such as Mvh, Dazl, Prdm14, Stella, Scp1, Scp3, Stra8 and Rec8 In contrast, for cells cultured in control medium, the activation of the above genes barely occurred. In addition, RA with SSC conditions yielded colonies of Acrosin-expressing cells and the positive ratio reached a peak at day 6. Our work thus establishes a simple and cost-efficient approach for male germ like cell differentiation from mouse PSCs and may propose a useful strategy for studying spermatogenesis in vitro.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , Células Germinativas/fisiologia , Células-Tronco/fisiologia , Tretinoína/farmacologia , Adulto , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Masculino , Camundongos , Espermatogênese/fisiologia
15.
J Colloid Interface Sci ; 473: 112-9, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27061362

RESUMO

Novel Bi4O5Br2 photocatalysts were synthesized by a one-pot solvothermal method in the presence of reactable ionic liquid 1-hexadecyl-3-methylimidazolium bromide ([C16mim]Br). X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (DRS) and other characterizations were applied to investigate their structures, morphologies, optical and electronic properties. Bisphenol-A (BPA) was chosen to evaluate the photocatalytic activity of Bi4O5Br2 nanosheets. After the visible light irradiation, about 91.2% of BPA were removed by Bi4O5Br2 after 3.5h with the reaction rate constant of 0.01086, which is much higher than that of the pure BiOBr (24.4%). Liquid chromatography combined with mass spectrometry (LC-MS) technique was used to track the intermediates species, showing the photocatalytic mechanism is related to photogenerated holes instead of hydroxyl radicals. The as-prepared Bi4O5Br2 also exhibited excellent stability as well as reusability, implying a great promising practical application for the photodegradation of organic pollutants.

16.
Dalton Trans ; 43(41): 15429-38, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25190481

RESUMO

Novel sphere-like MoS2/BiOBr composites were prepared by a facile ethylene glycol (EG)-assisted solvothermal process in the presence of the ionic liquid 1-hexadecyl-3-methylimidazolium bromide ([C16mim]Br). A nanostructured heterojunction, with few-layer MoS2 deposited on the surface of BiOBr microspheres, was constructed. During the synthetic process, the ionic liquid acted as a reactant, a template and a dispersing agent at the same time, leading to the formation of few-layer MoS2 dispersed on the surface of BiOBr microspheres. The MoS2/BiOBr composites exhibited much higher visible light photocatalytic activity towards rhodamine B (RhB) photodegradation than pure BiOBr. 3 wt% MoS2/BiOBr possessed the optimal photocatalytic activity, which was approximately 2.5 times as high as that of pure BiOBr. Through multiple characterization techniques, the relationship between the specific structure and the admirable photocatalytic activity of the MoS2/BiOBr microspheres was investigated. The critical role of the few-layer MoS2 in the MoS2/BiOBr microspheres was explored. A photocatalytic mechanism for the MoS2/BiOBr composites was also proposed.

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