Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cell Mol Biol Lett ; 24: 56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462899

RESUMO

[This corrects the article DOI: 10.1186/s11658-019-0167-8.].

2.
Mater Sci Eng C Mater Biol Appl ; 103: 109786, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349454

RESUMO

The purpose of our research was to verify the feasibility and effectiveness of a novel three-dimensional printed biopolymer device (3DP-BPD) for duct-to-mucosa pancreaticojejunostomy (PJ) in minipigs. Polylactic acid (PLA) was selected as the raw materials for 3DP-BPD. Three components of a 3DP-BPD were designed and manufactured: hollow stent, supporting disk, and nut. A pancreatic duct dilation model was developed in six minipigs. After 4 weeks, minipigs underwent operations with duct-to-mucosa PJ using 3DP-BPD. The operation time and postoperative complications were analyzed. The anastomotic sites were evaluated grossly 4 weeks and 24 weeks after PJ, and the histological evaluation of anastomotic sites was performed 24 weeks after PJ. The operation time of six stitches duct-to-mucosa PJ was 9.1 ±â€¯1.7 min. All minipigs survived without any adverse events like postoperative pancreatic fistula (POPF). Serum C reactive protein (CRP) and procalcitonin (PCT) levels were normal, and the anastomotic sites were connected tightly on gross observation and touch at 4 weeks and 24 weeks. Histological examinations indicated that the tissues were continuous between the pancreas and the jejunum. The use of 3DP-BPD did not increase the risk of severe local inflammation and POPF. 3DP-BPD used for duct-to-mucosa PJ is more convenient and clinically feasible for pancreatoenteric reconstruction.

3.
Cell Mol Biol Lett ; 24: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236121

RESUMO

Background: Impairment of the blood-brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP). Mesenchymal stem cells (MSCs) have been widely adopted in clinical research because of their pleiotropic functions. The aim of this study was to investigate the impact of MSCs on BBB permeability in SAP and the potential mechanisms driving these effects. Methods: Sprague-Dawley rats were randomly assigned to the control, SAP and SAP+MSCs groups. Pancreatic impairment was assessed. The serum levels of amylase, TNF-α and IL-10, expression levels of claudin-5, Bax, Bcl-2 and MMP-9, and the BBB permeability were measured. Endothelial cell apoptosis was evaluated. Results: SAP rats showed BBB impairment with increased permeability and secondary cerebral edema, which was confirmed using the Evans blue assay and the calculation of the brain dry/wet ratio. Treatment with MSCs decreased the serum levels of amylase and TNF-α, increased the serum levels of IL-10, attenuated the apoptosis of brain microvascular endothelial cells, upregulated claudin-5 expression and downregulated MMP-9 expression. This treatment attenuated the increased BBB permeability in SAP rats. Conclusions: MSCs attenuated the impairment of the BBB and decreased its permeability, producing protective effects in SAP rats.


Assuntos
Barreira Hematoencefálica/metabolismo , Transplante de Células-Tronco Mesenquimais , Pancreatite/metabolismo , Pancreatite/terapia , Doença Aguda/terapia , Amilases/sangue , Animais , Apoptose , Claudina-5/sangue , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Interleucina-10/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Pancreatite/sangue , Permeabilidade , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
4.
Ann Surg ; 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30672792

RESUMO

OBJECTIVE: The aim of the study was to analyze the outcomes of patients who have undergone laparoscopic pancreaticoduodenectomy (LPD) in China. SUMMARY BACKGROUND DATA: LPD is being increasingly used worldwide, but an extensive, detailed, systematic, multicenter analysis of the procedure has not been performed. METHODS: We retrospectively reviewed 1029 consecutive patients who had undergone LPD between January 2010 and August 2016 in China. Univariate and multivariate analyses of patient demographics, changes in outcome over time, technical learning curves, and the relationship between hospital or surgeon volume and patient outcomes were performed. RESULTS: Among the 1029 patients, 61 (5.93%) required conversion to laparotomy. The median operation time (OT) was 441.34 minutes, and the major complications occurred in 511 patients (49.66%). There were 21 deaths (2.43%) within 30 days, and a total of 61 (5.93%) within 90 days. Discounting the effects of the early learning phase, critical parameters improved significantly with surgeons' experience with the procedure. Univariate and multivariate analyses revealed that the pancreatic anastomosis technique, preoperative biliary drainage method, and total bilirubin were linked to several outcome measures, including OT, estimated intraoperative blood loss, and mortality. Multicenter analyses of the learning curve revealed 3 phases, with proficiency thresholds at 40 and 104 cases. Higher hospital, department, and surgeon volume, as well as surgeon experience with minimally invasive surgery, were associated with a lower risk of surgical failure. CONCLUSIONS: LPD is technically safe and feasible, with acceptable rates of morbidity and mortality. Nonetheless, long learning curves, low-volume hospitals, and surgical inexperience are associated with higher rates of complications and mortality.

5.
J Exp Clin Cancer Res ; 37(1): 167, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041660

RESUMO

BACKGROUND: Aberrant expression of Wiskott-Aldrich syndrome protein interacting protein family member 1 (WIPF1) contributes to the invasion and metastasis of several malignancies. However, the role of WIPF1 in human pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. METHODS: Human pancreatic cancer samples from PDAC patients were collected for methylation analysis. Bioinformatic prediction program and luciferase reporter assay were used to identify microRNAs regulating WIPF1 expression. The association between WIPF1 expression and the overall survival (OS) of patients with PDAC was evaluated by using The Cancer Genome Atlas (TCGA) database. The roles of miR-141/200c and WIPF1 on the invasion and metastasis of PDAC cells were investigated both in vitro and in vivo. RESULTS: We found that compared to the surrounding non-cancerous tissues, there was significantly increased methylation of miR-200c and miR-141 in human PDAC tissues that resulted in their silencing, whereas the members of the other cluster of miR-200 family including miR-200a, miR-200b and miR-429 were hypomethylated. Our data show that forced expression of miR-141 or miR-200c suppressed invasion and metastasis of PDAC cells both in vitro and in xenograft and identified WIPF1 as a direct target of miR-141 and miR-200c. Both miR-141 and miR-200c inhibit WIPF1 by directly interacting with its 3'-untranslated region. Remarkably, silencing of WIPF1 blocked PDAC growth and metastasis both in vitro and in vivo, whereas forced WIPF1 overexpression antagonized the tumor suppressive effect of miR-141/200c. Additionally, by using TCGA database we showed that high expression of WIPF1 correlated with poor survival in patients with PDAC. Moreover, we show that miR-141 and miR-200c blocked YAP/TAZ expression by suppressing WIPF1. CONCLUSIONS: We have identified WIPF1 as an oncoprotein in PDAC and a direct target of miR-141/miR-200c. We have also defined the miR-141/200c-WIPF1-YAP/TAZ as a novel signaling pathway that is involved in the regulation of the invasion and metastasis of human PDAC cells.

6.
J Inflamm (Lond) ; 15: 4, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497350

RESUMO

Background: Impairment of the blood-brain barrier (BBB) in severe acute pancreatitis (SAP) could result in life-threatening pancreatic encephalopathy. Interleukin-10 (IL-10) is a classical cytokine that is well-known for its strong immunoregulatory and anti-inflammatory abilities. However, whether and how IL-10 protects the BBB in SAP are still unclear. Methods: This study includes in vivo experiments using a SAP rat model and in vitro experiments using an in vitro BBB model consisting of a monolayer of brain microvascular endothelial cells (BMECs). The study groups are divided into the control, SAP (in vivo)/TNF-α (in vitro), IL-10 treatment, IL-10 + signal transducer and activator of transcription 3 (STAT3) inhibitor S3I-201 treatment groups. Pancreatic pathological scores, serum amylase, serum TNF-α levels and BBB permeability by Evan's blue assay in SAP rat models were evaluated. BMEC apoptosis in SAP rats or induced by TNF-αin vitro was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, separately. Expression levels of claudin-5 and proteins involved in the STAT3 signaling pathway were measured by Western blotting. Location and changes of junctional structure of claudin-5 on BMECs were assessed by immunohistochemistry and immunofluorescence. Results: In vivo, IL-10 alleviated the severity of inflammation, attenuated the increased BBB permeability in SAP rat models by reducing BMEC apoptosis via the STAT3 pathway and ameliorated the down-regulation of claudin-5 expression in BMECs; in vitro, IL-10 improved BBB integrity against TNF-α by attenuating BMEC apoptosis via the STAT3 pathway, the impairment of tight junction structure and the down-regulation of claudin-5 expression in BMECs. Conclusions: IL-10 improves BBB properties in SAP by attenuating the down-regulation of claudin-5 expression and the impairment of tight junctions and by STAT3 pathway-mediated anti-apoptotic effects on BMECs.

7.
BMC Cancer ; 17(1): 708, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29096620

RESUMO

BACKGROUND: The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. METHODS: By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. RESULTS: An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. CONCLUSION: The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Metabolômica/métodos , Neoplasias Pancreáticas/metabolismo , Animais , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Estudos de Viabilidade , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ressonância Magnética Nuclear Biomolecular , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Prognóstico , Reprodutibilidade dos Testes , Transplante Heterólogo
8.
Oncotarget ; 8(37): 61264-61281, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977862

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for1H NMR spectroscopy followed by univariate and multivariate statistical analyses. As results, no obvious metabonomic difference was demonstrated in serum between the two models, however, the model- and cell strain-specific metabonomic differences were observed in tumor tissues. According to the KEGG analysis, ABC transporters, glycerophospholipid metabolism, purine metabolism and central carbon metabolism were identified to be the most significant components involved in metabonomic differences. Considering the methodological discrepancy in SX and OX models, such differences should be contributed to tumor microenvironment. In general, SX are not equivalent to OX models at molecular level. Subcutaneous transplantation displayed its inherent limitations though it offered a simple, inexpensive, reproducible and quantifiable advantage. And orthotopic transplantation may be favorable to simulate PDAC in patients due to its similar pathogenesis to human pancreatic cancer.

9.
J Inflamm (Lond) ; 14: 7, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28344516

RESUMO

BACKGROUND: Ulinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP. METHODS: We established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h. RESULTS: We showed that the tissue damage of pancreas and the mortality of the SAP rats were significantly reduced by ulinastatin. We also showed that in the SAP rats the frequencies of CD4+ T cells and Tregs, as well as the expressions of TGF-ß1, CTLA-4, and Foxp3 were decreased in the SAP animals while IL-1ß, IL-10 and TNF-α were significantly increased. Treatment with ulinastatin up-regulated the proportion of Tregs in CD4+ T cells and the expression of IL-10, Foxp3 and CTLA-4 in the SAP rats in a dose dependence fashion, while down-regulating the levels of L-1ß and TNF-α, myeloperoxidase (MPO) activity. CONCLUSIONS: Our findings suggest that ulinastatin alleviates inflammatory response and tissue damage in SAP rats by increasing the proportion of Tregs. Our study provides a new mechanism for the beneficial effect of ulinastatin in SAP rat model.

10.
Stem Cell Res Ther ; 8(1): 12, 2017 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-28115014

RESUMO

BACKGROUND: Acute necrotizing pancreatitis (ANP) is often complicated by multiple organ failure. The small intestine is frequently damaged during ANP. Capillary leakage in multiple organs during ANP is one of the most important causes of multiple organ dysfunction. Damage to the capillary endothelial barrier and impaired water transportation could lead to capillary leakage in ANP. METHODS: Sprague-Dawley (SD) rats were randomized into a control group, the ANP group, the culture media-treated group, or the bone marrow-derived mesenchymal stem cell (BMSC)-treated group (30 rats in each group). Ten rats in each group were sacrificed at 6, 12, and 24 h after induction of experimental models. Serum, ascites, pancreatic, and small intestinal samples were collected. The levels of serum and ascites albumin and amylases were measured, pancreatic histology was assessed, and the connection changes between vessel endothelial cells were evaluated using scanning electron microscopy (SEM). Capillary leakage in small intestinal tissue was observed visually by tracking fluorescein isothiocyanate (FITC)-albumin, and was measured by the Evans blue extravasation method. The location and expression of aquaporin 1 (AQP1) in the small intestine was analyzed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot. RESULTS: The outcomes showed that the level of serum and ascites amylase is elevated. Conversely, the level of serum albumin is decreased while ascites albumin is elevated. There is damage to pancreatic tissue, and the small intestinal capillary endothelial barrier was aggravated. Furthermore, the expression of AQP1 was reduced significantly after induced ANP. Following treatment with MSCs, the elevation of amylase and the decrease of serum albumin were inhibited, the damage to pancreatic tissue and the level of small intestinal capillary leakage was alleviated, and the downregulation of AQP1 was reversed. CONCLUSIONS: In conclusion, MSC therapy could alleviate small intestinal injury in rats with ANP, the mechanism of which might be related to reduction of damage to the small intestinal capillary endothelial barrier, and increased expression of AQP1 in the small intestine.


Assuntos
Células da Medula Óssea/metabolismo , Meios de Cultivo Condicionados/farmacologia , Transplante de Células-Tronco Mesenquimais , Pancreatite Necrosante Aguda/patologia , Amilases/sangue , Animais , Aquaporina 1/genética , Aquaporina 1/metabolismo , Ascite/metabolismo , Células da Medula Óssea/citologia , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/patologia , Intestino Delgado/lesões , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia Eletrônica de Varredura , Pâncreas/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Albumina Sérica/análise
11.
Int J Oncol ; 50(2): 567-574, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28035372

RESUMO

The incidence of small (≤2 cm), non-functioning pancreatic neuroendocrine tumors (NF-pNETs) increased in the last decades. Before making appropriate strategy for patients with NF-pNETs ≤2 cm, pathological confirmation is vital. Incidentally diagnosed, sporadic small NF-pNETs may bring aggressive behavior and poor prognosis, such as extrapancreatic extension, lymph nodal metastasis, distant metastasis and recurrence, even causing disease-related death. Understanding and formulating an appropriate strategy for the patients with sporadic small, non-functioning pancreatic neuroendocrine tumors have been controversial for some time. Although several studies have reported that patients with NF-pNETs ≤2 cm had less rate of malignant behavior compared with larger ones (>2 cm); and the surgery approach may leading to surgery-related pancreatic complications; but there is still a lack of level I evidence to convince surgeons to abandon all cases with sporadic small NF-pNETs. Based on an updated literature search and review, the members of the Chinese Study Group for Neuroendocrine Tumors (CSNET) from high-volume centers have reached a consensus on the issue of the management strategy for the sporadic small NF-pNETs. We recommend that, except for some selected patients with NF-pNETs <1 cm, incidentally discovered and unacceptable surgical risks, all others with NF-pNETs ≤2 cm should undergo tumor resection with lymph node dissection or at least lymph node sampling and careful postoperative surveillance.


Assuntos
Excisão de Linfonodo/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Consenso , Gerenciamento Clínico , Humanos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
12.
Int J Oncol ; 49(5): 1991-2000, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27826620

RESUMO

Pancreatic neuroendocrine neoplasms (p-NENs) are slowly growing tumors with frequent liver metastasis. There is a variety of approaches to treat non-functional p-NENs with synchronous liver metastasis (LM) which complicates the determination of optimal treatment. Based on updated literature review, we discussed the treatment strategy determinants for p-NEN with LM. According to the resectability of primary tumor, the WHO 2010 grade classification and the radiological type of liver metastasis, the CSNET group reached agreements on a number of issues, including the following. Prior to treatment, biopsy is required to confirm pathology. Liver biopsy is important for more accurate grading of tumor and percutaneous core needle biopsy is more available than EUS-FNA. In patients with unresectable primary, surgical resection for liver-metastatic lesions should be avoided. Curative surgery is recommended for G1/G2 p-NET with type I LM and R1 resection also seems to improve overall survival rate. Cytoreductive surgery is recommended for G1/G2 p-NET with type II LM in select patients, and should meet stated requirements. Surgical resection for G1/G2 p-NET with type III LM and p-NEC with LM should be avoided, and insufficient evidence exists to guide the surgical treatment of G3 p-NET with LM. Liver transplantation may be an option in highly select patients. In addition, the optimal time for surgical approach is still required for more evidence.


Assuntos
Neoplasias Hepáticas/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Guias de Prática Clínica como Assunto/normas , China , Consenso , Humanos , Neoplasias Hepáticas/secundário , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Taxa de Sobrevida , Resultado do Tratamento
13.
Mol Biosyst ; 12(9): 2883-92, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27400832

RESUMO

Pancreatic cancer is a highly malignant disease with a poor prognosis and it is essential to diagnose and treat the disease at an early stage. The aim of this study was to understand the underlying biochemical mechanisms of pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and to identify potential serum biomarkers for early detection of pancreatic cancer. 7,12-Dimethylbenz(a)anthracene (DMBA)-induced PanIN and PDAC rat models were established and the serum samples were collected. The serum samples were measured using (1)H nuclear magnetic resonance (NMR) spectroscopy and analyzed by chemometric methods including principal component analysis (PCA) and (orthogonal) partial least squares discriminant analysis ((O)PLS-DA). The related biochemical pathways were derived from KEGG analysis of the significantly different metabolites. As results, some serum metabolites demonstrated alarming metabolic changes in the precursor lesion of pancreatic cancer (PanIN-2 in this study). These changes involved elevated levels of ketone compounds including 3-hydroxybutyrate, acetoacetate, and acetone, some amino acids including asparagine, glutamate, threonine, and phenylalanine, glycoproteins and lipoproteins including N-acetylglycoprotein, LDL and VLDL, and some metabolites that have been shown to contribute to mutagenicity and cancer promotion such as deoxyguanosine and cytidine. More metabolites were shown to be significantly different between PanIN and PDAC, suggesting that a more complex set of changes occurs from noninvasive precursor lesion to invasive cancer. The serum metabonomic changes of rats with PanIN and PDAC may extend our understanding of pancreatic molecular pathogenesis, and the metabolic variations from PanIN to PDAC will be helpful to understand evolution processes of the pancreatic disease. NMR-based metabonomic analysis of animal models will be beneficial for the human study and will be helpful for the early detection of pancreatic cancer.


Assuntos
Biomarcadores Tumorais , Carcinoma Ductal Pancreático/sangue , Metaboloma , Metabolômica , Animais , Carcinoma Ductal Pancreático/diagnóstico , Detecção Precoce de Câncer , Humanos , Imuno-Histoquímica , Masculino , Redes e Vias Metabólicas , Metabolômica/métodos , Estadiamento de Neoplasias , Espectroscopia de Prótons por Ressonância Magnética , Ratos
14.
Cancer Sci ; 107(6): 836-45, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27019331

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and is difficult to diagnose in the early phase. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in the early diagnosis of PDAC. In the present study, the animal models were established by embedding 7,12-dimethylbenzanthracene (DMBA) in the pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, (1) H nuclear magnetic resonance (NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. Pattern recognition models were successfully established and differential metabolites, including glucose, amino acids, carboxylic acids and coenzymes, were screened out. Compared with the control, the trends in the variation of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, thus, could served as biomarkers to distinguish PanIN from PDAC. Our results suggest that NMR-based techniques combined with multivariate statistical analysis can distinguish the metabolic differences among PanIN, PDAC and normal tissues, and, therefore, present a promising approach for physiopathologic metabolism investigations and early diagnoses of PDAC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Metabolômica , Neoplasias Pancreáticas/metabolismo , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Carcinoma in Situ/sangue , Carcinoma Ductal Pancreático/sangue , Detecção Precoce de Câncer , Espectroscopia de Ressonância Magnética , Masculino , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/sangue , Ratos , Ratos Sprague-Dawley
15.
Ultrastruct Pathol ; 40(1): 33-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26512751

RESUMO

This study examined the ultrastructural changes in the pulmonary mechanical barriers in a rat model of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). Animals were randomized into the SAP group (n = 60) and the control group (n = 60). SAP was induced by retrograde injection of 5% taurocholic acid into the biliopancreatic duct. The morphological abnormalities assessed by histology and the lung wet/dry weight ratio and the ultrastructural abnormalities assessed by transmission electron microscope and scanning electron microscope examinations plus lanthanum nitrate tracing were compared between the two groups at 6, 12, and 24 h post-SAP induction (n = 10/group/time point). The SAP group had significantly greater extravascular effusion than the control group at each time point as assessed by the lung wet/dry weight ratio (p < .001). The severity of the tissue damage increased in the lung and pancreas over time in the SAP group (all p < .001). In the SAP group, ultrastructural damages to the endothelial, epithelial, and pleural barriers were apparent and the damages to the endothelial barrier were detected earlier than the other two barriers, suggesting its fundamental role in preventing the further development of SAP-associated ALI. Moreover, the ultrastructural abnormalities were detected earlier than symptoms and morphological changes. The ultrastructural damages in the endothelial, epithelial, and pleural barriers occurred in the early stage of SAP. The endothelial barrier is likely to be the first line to prevent the further development in this rat model of SAP-associated ALI.


Assuntos
Lesão Pulmonar Aguda/patologia , Lesão Pulmonar/patologia , Pulmão/ultraestrutura , Pancreatite/patologia , Fator de Necrose Tumoral alfa/ultraestrutura , Lesão Pulmonar Aguda/diagnóstico , Animais , Modelos Animais de Doenças , Pulmão/patologia , Masculino , Microscopia Eletrônica de Transmissão/métodos , Ratos Sprague-Dawley
16.
Anal Biochem ; 477: 105-14, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25728943

RESUMO

Metabonomics has been applied in many bio-related scientific fields. Nevertheless, some animal research works are shown to fail when they are extended to humans. Therefore, it is essential to figure out suitable animal modeling to mimic human metabolism so that animal findings can serve humans. In this study, two kinds of commonly selected body fluids, serum and urine, from humans and various experimental animals were characterized by integration of nuclear magnetic resonance (NMR) spectroscopy with multivariate statistical analysis to identify the interspecies metabolic differences and similarities at a baseline physiological status. Our results highlight that the dairy cow and pig may be an optimal choice for transportation and biodistribution studies of drugs and that the Kunming (KM) mouse model may be the most effective for excretion studies of drugs, whereas the Sprague-Dawley (SD) rat could be the most suitable candidate for animal modeling under overall considerations. The biochemical pathways analyses further provide an interconnection between genetic evolution and metabolic variations, where species evolution most strongly affects microbial biodiversity and, consequently, has effects on the species-specific biological substances of biosynthesis and corresponding biological activities. Knowledge of the metabolic effects from species difference will enable the construction of better models for disease diagnosis, drug metabolism, and toxicology research.


Assuntos
Evolução Molecular , Metabolômica , Animais , Análise Química do Sangue , Humanos , Espectroscopia de Ressonância Magnética , Análise de Componente Principal , Especificidade da Espécie , Urinálise
17.
Oncol Rep ; 33(1): 383-90, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25394408

RESUMO

A gemcitabine (GEM)-resistant human pancreatic cancer cell line (PANC-1RG7) was established in vitro by gradually increasing GEM concentrations and cloning cell cultures to develop a cellular model of acquired drug resistance studies. We found that PANC-1RG7 cells exhibited significantly different morphological characteristics from parental cells. PANC-1RG7 cells grew slowly (p<0.05), yet the cell cycle remained unchanged (p>0.05). PANC-1RG7, with a resistance index to GEM of 39.9, showed cross-resistance characteristics to methotrexate, gefitinib, cisplatin and 5-fluorouracil. The proliferation inhibition of GEM was significantly reduced in vivo (p<0.05). The known resistance-associated genes and proteins we detected remained unchanged, with the exception of cytidine deaminase, multidrug resistance-related protein and breast cancer resistance protein genes, which decreased; by contrast, 5'-nucleotidase, ribonucleotide reductase (RRM) 1 and RRM2 proteins increased (p<0.05). Therefore, a cell line with acquired GEM resistance was established successfully. Resistance was acquired by overexpressing RRM1 and RRM2 proteins.


Assuntos
Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Ribonucleotídeo Redutases/metabolismo , Animais , Antimetabólitos Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/ultraestrutura , Cisplatino/farmacologia , Desoxicitidina/farmacologia , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Ribonucleosídeo Difosfato Redutase/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Oncol Lett ; 8(5): 2209-2214, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25295110

RESUMO

The present study aimed to analyze the characteristics of polyethylene glycol (PEG)ylated carboplatin liposomes (PL-CBPs), including size, stability, their release, entrapping and loading efficiencies, and their antitumor and antimetastatic effects on the lymph nodes. The PL-CBPs were prepared using PEG-2000 with the thin film hydration method. The liposome size and release, entrapping and loading efficiencies were detected by ultra-violet/visible spectrophotometry. A nude mouse model was established with the SGC-7901 gastric cell line to evaluate the antitumor effect of the PL-CBP. After 7 days, the mice were randomly divided into three groups (the control, CBP, and PL-CBP groups). CBP and PL-CBP were administered at a dose of 10 mg/kg for two consecutive cycles of treatment, 5 days apart, to their respective groups. In each group, two doses of 5 mg/kg were administered every 48 h. The tumor weight and volume were detected, and the food intake and body weight were measured during the administration. Apoptosis in the tumor cells was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and platinum (Pt) accumulation was detected by atomic absorption spectroscopy. Lastly, lymph node metastasis was evaluated by hematoxylin and eosin staining. The PL-CBPs were more stable when comapred with CBP alone, and the drug release efficiency was 0.7, 22.5, 48.7 and 65.1% at 37°C for 0, 12, 24 and 48 h. The results showed that the encapsulation efficiency was 85% and the loading efficiency was 0.15 mg/mg lipid. After 35 days, PL-CBP induced potent antitumor effects compared with the control and CBP groups (PL-CBP vs. control, P<0.01; PL-CBP vs. CBP, P<0.05). PL-CBP and CBP induced a lower and the lowest body weight and level of food intake, respectively, compared with the control group (CBP vs. control, P<0.05). The apoptosis rate and lymph node metastasis in the PL-CBP group was higher than that in the CBP and control groups (PL-CBP vs. control, P<0.01; PL-CBP vs. CBP, P<0.05). Pt accumulation in the tumors was higher in the PL-CBP group than in the CBP group (PL-CBP vs. CBP, P<0.05). The PL-CBPs were more stable in the circulation and could be released more slowly at the tumor site than compared with CBP injection. The PL-CBPs showed potent antitumor and antimetastatic effects on the lymph nodes.

19.
Pancreas ; 43(2): 291-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24518510

RESUMO

OBJECTIVES: To investigate the inhibition of PANC-1 pancreatic cancer cell growth by cucurmosin (CUS) and its possible mechanism. METHODS: We observed the inhibition of PANC-1 cell growth by sulforhodamine B and colony-forming experiments in vitro and established nonobese diabetic/severe combined immunodeficiency mouse subcutaneous tumor models in vivo. We used Western blot to analyze protein levels related to apoptosis and epidermal growth factor receptor (EGFR) signaling pathways after drug intervention, whereas the messenger RNA expression of EGFR was analyzed by quantitative real-time polymerase chain reaction. RESULTS: Sulforhodamine B and colony-forming experiments indicated that CUS inhibited PANC-1 cell proliferation in a dose- and time-dependent manner. A stronger inhibitory effect was observed when CUS was combined with gefitinib. The subcutaneous tumor growth was also inhibited. Western blot showed that all the examined proteins decreased, except for 4E-BP1 and the active fragments of caspase 3 and caspase 9 increased. Epidermal growth factor receptor expression did not change significantly in quantitative real-time polymerase chain reaction. CONCLUSIONS: Cucurmosin can strongly inhibit the growth of PANC-1 cells in vitro and in vivo. Cucurmosin can down-regulate EGFR protein expression, but not at the messenger RNA level. Cucurmosin can also inhibit the ras/raf and phosphatidylinositol 3-kinase/Akt downstream signaling pathways and enhance the sensitivity of the EGFR-targeted drug gefitinib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas de Plantas/farmacologia , Quinazolinas/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Caspases/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Gefitinibe , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas de Plantas/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinazolinas/administração & dosagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Inativadoras de Ribossomos Tipo 1/administração & dosagem , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Exp Biol Med (Maywood) ; 238(6): 687-95, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23918880

RESUMO

The aim of this study was to preliminarily investigate the effect of bone marrow mesenchymal stem cells (MSCs) on structural change of capillary endothelial barrier and expression variation of aquaporin 1 (AQP1) in kidney at the onset of renal injury caused by severe acute pancreatitis (SAP). Ninety male Sprague-Dawley (SD) rats were divided into the control group, the SAP group in which animals received induction of SAP and the MSCs-treated group in which SAP-induced animals were injected with MSCs. They were further subdivided according to the time point that the animals were killed; 6 h, 12 h and 24 h after the closure of the incision, serum, pancreatic and renal samples were collected, respectively. The level of serum amylase (AMY), creatinine (Cr) and blood urea nitrogen (BUN) were analysed, the change of pancreatic histology was assessed, the structural change of the renal interstitial capillaries was evaluated using the transmission electron microscope (TEM) and the location and expression of AQP1 in kidney were analysed using immunohistochemistry, quantitative polymerase chain reaction and Western blot. The outcomes showed that the level of serum AMY, Cr, BUN elevated, the damage of pancreatic tissue and renal capillary endothelial barrier was aggravated and the expression of AQP1 was reduced significantly after induced pancreatitis. But after treatments with MSCs, the elevation of AMY, Cr and BUN was inhibited, the damage of pancreatic tissue and renal interstitial capillary barrier was alleviated and the down-regulation of AQP1 was reversed. In summary, the MSCs therapy could alleviate renal injury in rats with SAP, the mechanism of which might be related to reduction of the damage to renal interstitial capillary endothelial barrier, and up-expression of AQP1 in kidney.


Assuntos
Lesão Renal Aguda/terapia , Transplante de Células-Tronco Mesenquimais , Pancreatite/complicações , Lesão Renal Aguda/complicações , Lesão Renal Aguda/patologia , Amilases/sangue , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais/métodos , Pancreatite/patologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA