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1.
Cell Death Dis ; 10(8): 588, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383854

RESUMO

ZIP4 is a zinc transporter involved in epithelial cell morphology and migration in various cancers. In the epithelial-to-mesenchymal transition (EMT), epithelial cells transition into mesenchymal cells. The EMT plays a crucial role in invasiveness and metastasis during tumorigenesis. The aim of this study was to investigate the role of ZIP4 in the invasiveness and radiosensitivity of human nasopharyngeal carcinoma (NPC). In this study, results from 99 human patients with NPC showed that ZIP4 expression levels significantly correlated with a higher TN (tumor, lymph node) classification, as well as shorter overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Forced overexpression of ZIP4 promoted the migration and invasion of C666-1 cells through regulation of the EMT process. In contrast, ZIP4 silencing by lentivirus-mediated shRNA inhibited the EMT and metastasis of C666-1 cells in vitro and in vivo. Importantly, protein microarray analyses showed that downregulation of ZIP4 in C666-1 cells resulted in the decreased abundance of phosphoinositide 3-kinase (PI3K) p85 (Tyr607), phosphorylated (p)-Akt (Ser473), phosphorylated (p)-Akt (Thr308), and phosphorylated glycogen synthase kinase 3ß (pGSK3ß; Ser9). These data suggest that ZIP4 induces the EMT and promotes migration and invasion via the PI3K/Akt signaling pathway in NPC. Moreover, ZIP4 silencing significantly enhanced radiation-induced apoptosis and growth inhibition of human C666-1 cells in vitro and enhanced the antitumor activity of ionizing radiation (IR), leading to tumor growth inhibition in vivo. These results demonstrate that ZIP4 is a novel prognostic factor for malignant NPC progression. More importantly, targeting ZIP4, along with radiotherapy, may be an effective new treatment for NPC.

2.
Int J Environ Health Res ; : 1-9, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184496

RESUMO

To evaluate the association between ambient air pollution and hyperuricemia, we prospectively followed 1748 traffic police officers without hyperuricemia at baseline (2009-2014) from 11 districts in Guangzhou, China. We calculated six-year average PM10, SO2 and NO2 concentrations using data collected from air monitoring stations. The hazard ratios for hyperuricemia per 10 µg/m3 increase in air pollutants were 1.46 (95% CI: 1.28-1.68) for PM10, 1.23 (95% CI: 1.00-1.51) for SO2, and 1.43 (95% CI: 1.26-1.61) for NO2. We also identified changes in the ratio of serum uric acid to serum creatinine concentrations (ua/cre) per 10 µg/m3 increase in air pollutants as 11.54% (95% CI: 8.14%-14.93%) higher for PM10, 5.09% (95% CI: 2.76%-7.42%) higher for SO2, and 5.13% (95% CI: 2.35%-7.92%) higher for NO2, respectively. Long-term exposure to ambient air pollution was associated with a higher incidence of hyperuricemia and an increase in ua/cre among traffic police officers.

3.
J Nanobiotechnology ; 17(1): 54, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992018

RESUMO

BACKGROUND: Nanomaterials that exhibit intrinsic enzyme-like characteristics have shown great promise as potential antibacterial agents. However, many of them exhibit inefficient antibacterial activity and biosafety problems that limit their usefulness. The development of new nanomaterials with good biocompatibility and rapid bactericidal effects is therefore highly desirable. Here, we show a new type of terbium oxide nanoparticles (Tb4O7 NPs) with intrinsic oxidase-like activity for in vitro and in vivo antibacterial application. RESULTS: We find that Tb4O7 NPs can quickly oxidize a series of organic substrates in the absence of hydrogen peroxide. The oxidase-like capacity of Tb4O7 NPs allows these NPs to consume antioxidant biomolecules and generate reactive oxygen species to disable bacteria in vitro. Moreover, the in vivo experiments showed that Tb4O7 NPs are efficacious in wound-healing and are protective of normal tissues. CONCLUSIONS: Our results reveal that Tb4O7 NPs have intrinsic oxidase-like activity and show effective antibacterial ability both in vitro and in vivo. These findings demonstrate that Tb4O7 NPs are effective antibacterial agents and may have a potential application in wound healing.


Assuntos
Antibacterianos/química , Escherichia coli , Nanopartículas Metálicas/química , Óxidos/química , Oxirredutases/química , Staphylococcus aureus , Térbio/química , Cicatrização , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Sobrevivência Celular , Escherichia coli/efeitos dos fármacos , Hemólise , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos Endogâmicos BALB C , Óxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Térbio/farmacologia
4.
Future Med Chem ; 11(9): 959-974, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30789758

RESUMO

Aim: Bladder cancer is a highly recurrent urologic malignancy with limited treatment approaches. Previously, we reported compound 11 is a FGFR3 inhibitor with significant antibladder cancer activity. Materials & methods: In this study, a series of 7H-pyrrolo-[2,3-d]pyrimidine derivatives were synthesized through ring formation and modification of compound 11 for anticancer activity evaluation. Results: Compound 13i is the most effective agent against human RT-112 bladder cancer cells. Notably, 13i strongly inhibits CK1δ without affecting FGFR3 activity. We generated 13i HCl to increase solubility and showed profound cell cycle accumulation at the sub-G1 phase and apoptosis in CK1δ-overexpressed bladder and ovarian cancer cells. Conclusion: These results indicate that compound 13i could be a lead compound for further development of novel anticancer agents.

5.
Doc Ophthalmol ; 138(2): 137-145, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739234

RESUMO

OBJECTIVE: To assess the role of multifocal electroretinograms (mfERGs) and optical coherence tomography (OCT) for detecting early changes in macular functions of patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: mfERGs and OCT were used to examine a NPC group (36 NPC patients after radiotherapy without clinically visible radiation retinopathy, 36 eyes) and a normal control group (25 healthy individuals, 25 eyes) with the same procedure and parameters. The two groups of mfERG were summarized by calculating ring averages, response density, N1 amplitude and P1 and N1 latencies were analysed. OCT scan thickness was summarized into ETDRS regions for comparison. RESULTS: Compared with controls, the NPC group had significantly decreased P1 response densities in 1-4 ring regions and N1 amplitudes in 1-3 rings (P < 0.01). P1 latencies were obviously prolonged in rings 1 (P < 0.01). In four quadrants (inferonasal, superonasal, inferotemporal and superotemporal) of the mfERG response waveforms, the NPC group had significantly decreased P1 response densities and N1 amplitudes mainly in the inferonasal and inferotemporal quadrants, showing statistically significant differences from the control group (P < 0.0125). But for the OCT results, there is no statistically significant difference between the NPC group and the control group. CONCLUSIONS: In NPC patients after radiotherapy, there may be changes in the mfERGs before any visible fundus lesions appeared as radiation macular oedema. Since the global OCT macular thickness analysis cannot reveal early changes, the mfERGs can objectively and quantitatively assess the earlier changes in macular function in NPC patients.


Assuntos
Eletrorretinografia/métodos , Carcinoma Nasofaríngeo/radioterapia , Lesões por Radiação/fisiopatologia , Radioterapia/efeitos adversos , Retina/efeitos da radiação , Adulto , Idoso , Feminino , Fundo de Olho , Humanos , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Retina/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia
6.
World J Gastroenterol ; 25(1): 138-150, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30643364

RESUMO

AIM: To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and classification were correlated with patient clinicopathological features and outcomes. RESULTS: CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage (P < 0.01) and distant metastasis (P < 0.01). Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation (P < 0.01). CONCLUSION: Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/patologia , Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes/patologia , Neoplasias Pancreáticas/patologia , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Molécula de Adesão da Célula Epitelial/análise , Feminino , Humanos , Estimativa de Kaplan-Meier , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Prognóstico , Proteína 1 Relacionada a Twist/análise , Vimentina/análise
7.
Sci Rep ; 9(1): 328, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674924

RESUMO

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in children in developed countries. However, little is known regarding the role of transcriptomic targets of KD in the disease progression and development of complications, especially coronary artery aneurysms (CAA). The aim of our study was to identify transcripts affected by KD and their potential role in the disease. We enrolled 37 KD patients and collected blood samples along a comprehensive time-course. mRNA profiling demonstrated an abundance of CD177 transcript in acute KD, and in the intravenous immunoglobulin (IVIG)-resistant group compared to in the IVIG-sensitive group. lncRNA profiling identified XLOC_006277 as the most highly expressed molecule. XLOC_006277 expression in patients at acute stage was 3.3-fold higher relative to patients with convalescent KD. Moreover, XLOC_006277 abundance increased significantly in patients with CAA. XLOC_006277 knockdown suppressed MMP-8 and MMP-9 expression, both associated with heart lesions. Our result suggested that the increase of CD177pos neutrophils was associated with KD. Moreover, this study provided global long non-coding RNA transcripts in the blood of patients with KD, IVIG-resistant KD, or CAA. Notably, XLOC_006277 abundance was associated with CAA, which might contribute to further understanding of CAA pathogenesis in KD.

8.
Strahlenther Onkol ; 195(6): 457-467, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30689027

RESUMO

PURPOSE: To investigate the swallowing status and its impact on quality of life (QOL) in patients who underwent radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: In this study, 334 patients with NPC who underwent radiotherapy were reviewed. Clinical characteristics, videofluoroscopic swallowing studies (VFSSs), and scores of the World Health Organization quality of life-BREF (WHOQOL-BREF) were retrospectively analyzed for all patients. RESULTS: In this study, 143 of 334 (42.8%) patients showed dysphagia. The nodular stage N3 of NPC, neoadjuvant and concurrent chemotherapy were clinical predictors for dysphagia. VFSS of patients with dysphagia showed a high incidence of vallecular residue (100%), apraxia (99%), premature bolus loss (98%), bolus formation (98%), pyriform sinus residue (95%), and mastication (94%). Moreover, WHOQOL-BREF scores for the physical health, psychological, and environment domains were lower of the dysphagia group than those of the control group (P < 0.01). Videofluoroscopic dysphagia scale scores showed significant negative correlations with scores for the physical health (R = -0.66, P < 0.01), psychological (R = -0.70, P < 0.01), social relationships (R = -0.56, P < 0.01), and environment (R = -0.61, P < 0.01) domains of WHOQOL-BREF. CONCLUSIONS: Radiotherapy-induced dysphagia is common in NPC patients and is correlated with poor quality of life. Patients, caregivers, and clinical physicians should be aware of these adverse effects and provide timely treatment for radiotherapy-induced dysphagia in collaboration with cross-disciplinary colleagues.

9.
J Asian Nat Prod Res ; : 1-12, 2018 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-30394104

RESUMO

Microarray expression profiles of lncRNAs and mRNAs were investigated in HepG2 cells treated with 20 µg/ml ginsenoside Rh2 as well as in ginsenoside Rh2-untreated cells. Microarray analysis showed 618 upregulated lncRNAs and 161 downregulated lncRNAs in HepG2 cells treated with ginsenoside Rh2 compared with the control group. Moreover, three differentially expressed lncRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This may be beneficial to patients as an anti-cancer treatment and potentially provide novel targets for HCC (hepatocellular carcinoma) therapy.

10.
Eur J Med Chem ; 162: 612-630, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30476825

RESUMO

We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC50 value of 1.1 µM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model.

11.
Cell Death Dis ; 9(11): 1065, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30337520

RESUMO

Cancer-associated fibroblasts (CAFs), a dominant component of the pancreatic tumor microenvironment, are mainly considered as promotors of malignant progression, but the underlying molecular mechanism remains unclear. Here, we show that SDF-1 secreted by CAFs stimulates malignant progression and gemcitabine resistance in pancreatic cancer, partially owing to paracrine induction of SATB-1 in pancreatic cancer cells. CAF-secreted SDF-1 upregulated the expression of SATB-1 in pancreatic cancer cells, which contributed to the maintenance of CAF properties, forming a reciprocal feedback loop. SATB-1 was verified to be overexpressed in human pancreatic cancer tissues and cell lines by quantitative real-time PCR, western blot, and immunohistochemical staining, which correlated with tumor progression and clinical prognosis in pancreatic cancer patients. We found that SATB-1 knockdown inhibited proliferation, migration, and invasion in SW1990 and PANC-1 cells in vitro, whereas overexpression of SATB-1 in Capan-2 and BxPC-3 cells had the opposite effect. Immunofluorescence staining showed that conditioned medium from SW1990 cells expressing SATB-1 maintained the local supportive function of CAFs. Furthermore, downregulation of SATB-1 inhibited tumor growth in mouse xenograft models. In addition, we found that overexpression of SATB-1 in pancreatic cancer cells participated in the process of gemcitabine resistance. Finally, we investigated the clinical correlations between SDF-1 and SATB-1 in human pancreatic cancer specimens. In summary, these findings demonstrated that the SDF-1/CXCR4/SATB-1 axis may be a potential new target of clinical interventions for pancreatic cancer patients.

12.
Int J Gynecol Cancer ; 28(7): 1325-1332, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30074519

RESUMO

OBJECTIVES: The optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages. METHODS: We performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2-IIA. RESULTS: For patients with stage IA2-IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2-IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2-IIA. CONCLUSIONS: In cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

14.
Chin J Cancer Res ; 30(3): 307-314, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30046225

RESUMO

Objective: The radioprotective effects of amifostine remain uncertain in patients with nasopharyngeal carcinoma (NPC), and adverse effects and cost limit generalization of its classical everyday regimen. This phase II multicenter randomized controlled trial aimed to explore whether amifostine could ameliorate the toxicities of NPC patients in the era of intensity-modulated radiotherapy (IMRT), and to compare different regimens of amifostine on effectiveness and safety. Methods: Patients with stage I-IVB NPC were involved prospectively from January 1st, 2013. All patients received radical treatment based on IMRT. After a randomization stratified by their stage, these patients were allocated into 3 groups: the group treated without amifostine, the group treated with the everyday regimen of amifostine, and the group treated with the every-other-day regimen. The 3 groups of patients were compared on radiotherapy-related acute toxicities, treatment effects of NPC, and amifostine-related complications. This trial was registered on the clinicaltrials.gov (ID: NCT01762514). Results: Until August 31st, 2017, totally 187 patients completed experimental intervention. Only amifostine of everyday regimen appeared to reduce the patient proportion of mucositis (79.1% vs. 96.8%, P=0.002). Hypocalcemia was less common in patients treated without amifostine than in those treated with amifostine (22.6% vs. 53.4% vs. 41.8%, P=0.002). Neither complete remission rates nor the survivals were affected by amifostine. Conclusions: Amifostine of everyday regimen could reduce mucositis in NPC patients who received IMRT, though it also had the possibility to cause more hypocalcemia.

15.
Int J Radiat Oncol Biol Phys ; 102(3): 552-555, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29960057

RESUMO

PURPOSE: Nasopharyngeal carcinoma (NPC) is a type of malignancy with a high prevalence in southern China and Southeast Asia. The primary treatment modality is radiation therapy (RT). Osteoradionecrosis (ORN) of the skull base remains one of the most serious complications after RT, affecting survival time and quality of life. Thus far, skull base ORN has been seldom reported and can be difficult to distinguish and easy to misdiagnose. In this retrospective study, we report the incidence of skull base ORN and analyze its associated factors in an attempt to decrease the occurrence of ORN. METHODS AND MATERIALS: From January 2001 to December 2012, a total of 1348 patients who received diagnoses of NPC received 1 course of RT. Complete medical records were reviewed, and the patients were examined by magnetic resonance imaging and nasopharyngeal endoscopy during follow-up after primary treatment. Patients with other tumors of the head and neck, a history of RT, failure to complete RT, and those lost to follow-up were excluded. Treatment was delivered with external beam RT using standard linear accelerators. RESULTS: A total of 1348 patients with NPC were enrolled in this study after 1 course of RT; among these patients, 14 received diagnoses of skull base ORN. The incidence of skull base ORN was 1.04%. The average latency interval from the completion of RT to the diagnosis of skull base ORN was 45.57 months. Skull base ORN after 1 course of RT was associated with the T stage; total radiation dose to the nasopharynx, including the skull base in the radiation field; and anemia. CONCLUSIONS: The occurrence of skull base ORN was associated with primary tumors with advanced T stages, high doses of nasopharynx RT, and radiation fields that included the skull base. These factors may be used as predictors for the incidence of skull base ORN.

16.
Sleep ; 41(9)2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29939357

RESUMO

Study Objectives: There is limited knowledge regarding the effects of air pollution on sleep disorders, particularly in children. The aim of this study is to investigate this association in Chinese children. Methods: During 2012-2013, 59754 children aged 2-17 years were randomly selected from 27 districts in seven northeastern Chinese cities. All participants' sleep was evaluated with the Sleep Disturbance Scale for Children. Four year average concentrations of pollutants were calculated for particles with an aerodynamic diameter of ≤1 µm (PM1), ≤2.5 µm (PM2.5) from a spatial statistical model, and ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) from monitoring stations. To examine the effects, two-level regression analysis was used, controlling for covariates. Results: We observed that sleep disorder was generally associated with all air pollutants, with the highest odds among PM1 exposure for male (odds ratio [OR] 1.55; 95% confidence interval [95% CI] 1.36-1.76) and female (OR 1.50; 95% CI 1.30-1.72) children. The overall strongest association with sleep disorder symptom was exposure to PM1 and Disorders of Excessive Somnolence (OR 1.43; 95% CI 1.30-1.58). PM1 and PM2.5 were strongly associated with all sleep disorder symptoms in females (ORs ranged for PM1 from 1.19 to 1.49; and PM2.5 1.18 to 1.44). The association between air pollutants and total sleep score was generally greater in female than in male children. Conclusions: Our findings suggest that exposure to air pollutants increases the odds of sleep disorder in children and point to the need to make reducing exposure to air pollutants a public health priority.

17.
Cell Death Dis ; 9(5): 453, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29670110

RESUMO

Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic cancer, partially owing to paracrine induction of VCAM-1 in pancreatic cancer cells. Reciprocally, VCAM-1-induced lactate production from pancreatic cancer cells with enhanced aerobic glycolysis activates macrophages to a TAM-like phenotype, forming a positive feedback loop. VCAM-1 was found to be highly expressed in human pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines, and is associated with disease progression and predicts clinical outcome in PDAC patients. Flow cytometry analysis further demonstrated that VCAM-1 downregulation induced an accumulation of PDAC cells in G0/G1 phase, accompanied by a significant decrease in S phase. Downregulation of VCAM-1 significantly inhibited proliferation, colony formation, migration, and invasion of PDAC cells in vitro, whereas the ectopic expression of VCAM-1 had the opposite effect. VCAM-1 on pancreatic cancer cells might tethers THP-1 monocytes to cancer cells via counter-receptor interaction, providing a survival advantage to pancreatic cancer cells that infiltrate leukocyte-rich microenvironments. Furthermore, downregulation of VCAM-1 could repress tumor growth in mouse xenograft models. In particular, our results highlighted the contribution of VCAM-1 to the maintenance of the Warburg effect in PDAC cells. Finally, we investigated the clinical correlations of CCL18 and VCAM-1 in human PDAC specimens. In summary, these findings indicate that the CCL18/PITPNM3/NF-kB/VCAM-1 regulatory network might provide a potential new therapeutic strategy for PDAC.

18.
Can J Gastroenterol Hepatol ; 2018: 6075207, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29623265

RESUMO

Background: The prognostic values of weight loss and body mass index (BMI) in esophageal carcinoma remain controversial. This study aimed to evaluate the impacts of weight loss on the survival of patients undergoing radical surgery and adjuvant chemotherapy. Methods: The medical records of 189 consecutive patients with nonmetastatic esophageal carcinoma treated in our hospital between January 2012 and December 2013 were reviewed, and 121 patients were included for analysis. Results: Kaplan-Meier analysis revealed that the 3-year overall survival rate was significantly higher in the low pretreatment weight loss (pre-LWL) group than in the high pretreatment weight loss (pre-HWL) group (P < 0.001). In addition, the 3-year overall survival rate of normal weight group was higher than that of overweight and underweight groups (P = 0.007). Multivariate Cox proportional hazards analysis showed that pre-LWL group had a significantly better 3-year overall survival than pre-HWL group (P = 0.027, HR = 1.89, and 95% CI = 1.07-3.32). pN stage and age were also the survival prognostic factors. Conclusions: Our study showed that low pretreatment weight loss predicted a better survival outcome in the esophageal carcinoma patients with radical surgery and adjuvant chemotherapy. However, BMI and weight loss during treatment had no impact on the survival outcome.

19.
Lancet Planet Health ; 2(2): e64-e73, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29615239

RESUMO

BACKGROUND: Health effects of air pollution on diabetes have been scarcely studied in developing countries. We aimed to explore the associations of long-term exposure to ambient particulate matter (PM) and gaseous pollutants with diabetes prevalence and glucose-homoeostasis markers in China. METHODS: Between April 1 and Dec 31, 2009, we recruited a total of 15 477 participants aged 18-74 years using a random number generator and a four-staged, stratified and cluster sampling strategy from a large cross-sectional study (the 33 Communities Chinese Health Study) from three cities in Liaoning province, northeastern China. Fasting and 2 h insulin and glucose concentrations and the homoeostasis model assessment of insulin resistance index and ß-cell function were used as glucose-homoeostasis markers. Diabetes was defined according to the American Diabetes Association's recommendations. We calculated exposure to air pollutants using data from monitoring stations (PM with an aerodynamic diameter of 10 µm or less [PM10], sulphur dioxide, nitrogen dioxide, and ozone) and a spatial statistical model (PM with an aerodynamic diameter of 1 µm or less [PM1] and 2·5 µm or less [PM2·5]). We used two-level logistic regression and linear regression analyses to assess associations between exposure and outcomes, controlling for confounders. FINDINGS: All the studied pollutants were significantly associated with increased diabetes prevalence (eg, the adjusted odds ratios associated with an increase in IQR for PM1, PM2·5, and PM10 were 1·13, 95% CI 1·04-1·22; 1·14, 1·03-1·25; and 1·20, 1·12-1·28, respectively). These air pollutants were also associated with higher concentrations of fasting glucose (0·04-0·09 mmol/L), 2 h glucose (0·10-0·19 mmol/L), and 2 h insulin (0·70-2·74 µU/L). No association was observed for the remaining biomarkers. Stratified analyses indicated greater effects on the individuals who were younger (<50 years) or overweight or obese. INTERPRETATION: Long-term exposure to air pollution was associated with increased risk of diabetes in a Chinese population, particularly in individuals who were younger or overweight or obese. FUNDING: The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, the Guangdong Province Natural Science Foundation, the Career Development Fellowship of Australian National Health and Medical Research Council, and the Early Career Fellowship of Australian National Health and Medical Research Council.

20.
Environ Pollut ; 238: 177-185, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29554565

RESUMO

The effect of ambient air pollution exposure on childhood hypertension has emerged as a concern in China, and previous studies suggested pet ownership is associated with lower blood pressure (BP). However, limited information exists on the interactive effects pet ownership and air pollution exposure has on hypertension. We investigated the interactions between exposure to pet ownership and air pollutants on hypertension in Chinese children. 9354 students in twenty-four elementary and middle schools (aged 5-17 years) in Northeastern China were evaluated during 2012-2013. Four-year average concentrations of particulate matter with aerodynamic diameter of ≤10 µm (PM10), SO2, NO2, and O3, were collected in the 24 districts from 2009 to 2012. Hypertension was defined as average diastolic or systolic BP (three time measurements) in the 95th percentile or higher based on height, age, and sex. To examine effects, two-level regression analysis was used, controlling covariates. Consistent interactions between exposure to pet and air pollutants were observed. Compared to children exposed to pet, those not exposed exhibited consistently stronger effects of air pollution. The highest odds ratios (ORs) per 30.6 µg/m3 increase in PM10 were 1.79 (95%confidence interval [95%CI]: 1.29-2.50) in children without current pet exposure compared to 1.24 (95%CI: 0.85-1.82) in children with current pet exposure. As for BP, only O3 had an interaction for all exposure to pet ownership types, and showed lower BP in children exposed to pet. The increases in mean diastolic BP per 46.3 µg/m3 increase in O3 were 0.60  mmHg (95%CI: 0.21, 0.48) in children without pet exposure in utero compared with 0.34  mmHg (95%CI: 0.21, 0.48) in their counterparts. When stratified by age, pet exposure was more protective among younger children. In conclusion, in this large population-based cohort, pet ownership is associated with smaller associations between air pollution and hypertension in children, suggesting pet ownership reduces susceptibility to the health effects of pollutants.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Hipertensão/epidemiologia , Animais de Estimação , Adolescente , Poluição do Ar/análise , Animais , Grupo com Ancestrais do Continente Asiático , Pressão Sanguínea , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Razão de Chances , Material Particulado/análise , Análise de Regressão
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