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1.
J Pharm Biomed Anal ; 234: 115525, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37320973

RESUMO

Gas chromatography-mass spectrometry (GC-MS) is the first choice for law enforcement agencies in various countries to analyze new psychoactive substances (NPS) because of its advantages and complete databases. For synthetic cathinone-type NPS (SCat), alkalization and extraction processes before GC-MS analysis are essential. However, the base form of SCat is unstable, causing it to quickly degrade in solution and cause pyrolysis at the GC-MS injection inlet. In this study, we investigated the degradation of ethyl acetate and pyrolysis at the GC-MS injection inlet of 2-fluoromethcathinone (2-FMC), the most unstable SCat. Using gas chromatography-quadruple/time-of-flight mass spectrometry (GC-Q/TOF-MS) combined with the predicted data from theoretical calculations and the analysis of mass spectrometry (MS) fragmentation, the structures of 15 2-FMC degradation and pyrolysis products were identified. Among them, 11 products were produced during degradation, and six products were obtained from pyrolysis (two of which were the same as the degradation products). At the same time, the degradation and pyrolysis pathways of 2-FMC were provided. The balance between keto-enol and enamine-imine tautomerism triggered the primary degradation pathway of 2-FMC. The subsequent degradation started from the tautomer with a hydroxyimine structure, including imine hydrolysis, oxidation, imine-enamine tautomerism, intramolecular ammonolysis of halobenzene, and hydration to generate a series of degradation products. The secondary degradation reaction was the ammonolysis of ethyl acetate to yield N-[1-(2'-fluorophenyl)-1-oxopropan-2-yl]-N-methylacetamide and the byproduct, N-[1-(2'-fluorophenyl)-1-oxopropan-2-yl]-N-methylformamide. In the pyrolysis of 2-FMC, the major reactions were dehydrogenation, intramolecular ammonolysis of halobenzene, and defluoromethane. The achievements of this manuscript not only study 2-FMC degradation and pyrolysis but also lay the foundation for the study of SCat stability and their accurate analysis by GC-MS.


Assuntos
Hidrocarbonetos Halogenados , Pirólise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Iminas
2.
J Anal Toxicol ; 47(5): 436-447, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-36947399

RESUMO

In this study, we used solid-phase extraction with liquid chromatography-ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS) to analyze 2-fluorodeschloroketamine (2-FDCK) metabolites in human urine. The complete set of oxidative metabolites was identified, with 17 compounds divided into four groups. Furthermore, we examined the hydroxy substitution site after oxidative metabolism with theoretical calculation and 2-FDCK nuclear magnetic resonance (NMR) data. We clarified the correlation of the oxidative metabolic sites with the electron cloud density in the structure. Additionally, two enantiomers of dihydro-2-fluorodeschloroketamine (dihydro-2-FDCK) were determined by using a laboratory-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via NMR spectrometry data prediction of the ACD Labs-Structure Elucidator Suite software and theoretical calculation. Moreover, the stereoselectivity of the related enzymes in hydrogenation metabolism in vivo was clarified. These findings provide an important reference for analyzing other oxidative metabolites, laying the foundation for future analysis, prediction, elucidation and identification of the latest ketamine-type new psychoactive substance metabolites.


Assuntos
Estresse Oxidativo , Humanos , Hidrogenação , Espectrometria de Massas , Cromatografia Líquida/métodos
3.
Int J Surg ; 104: 106718, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35724803

RESUMO

BACKGROUND: Recent interest in laparoscopic right colectomy with D3 lymphadenectomy for right colon cancer, has raised renewed attention to the anatomic variations of the gastrocolic trunk of Henlé (GTH). Understanding the vascular structure of the GTH region for individual patients should improve surgical outcomes. The goal of this nationwide multicenter study (Anatomical Classification of Henlé's Trunk in Laparoscopic Right Hemi-colectomy (HeLaRC) trial) was to study the anatomic patterns of the GTH region, to clarify the implications of GTH in laparoscopic right colectomy with D3 lymphadenectomy (D3-RC) and analyze their clinical significance. METHODS: We enrolled 583 patients from 26 centers across China who underwent D3-RC. The number of tributaries, length and types of GTH constitutions and their influence on intra-operative data were investigated. A nomogram score (based on the length of GTH, body mass index (BMI), tumor location, T stage and type of GTH (type I vs. non-type I) was established to assess the potential hazard of bleeding. RESULTS: The GTH was found in 567 patients (97.3%). The distribution of GTH types was 0 (14.1%, n = 80), I (53.3%, n = 302), II (27.0%, n = 153), III (5.6%, n = 32). Of note, the type I GTH, T1 stage and tumor location at ileocecal or ascending colon were correlated with shorter exposure time of the GTH region (P < 0.0001). Short length of GTH (P = 0.002) and tumor location (transverse colon vs. non transverse colon) (P = 0.003) were correlated with the amount of GTH bleeding during the surgery. Nomogram discrimination was good (C-index: 0.72 (95% CI: 0.64, 0.80)). The dissection plane was better in patients with type I GTH than with other types (P = 0.023). CONCLUSION: GTH pattern variations may affect surgical outcomes in patients undergoing D3-RC. Better recognition of GTH anatomy might lead to a safer operation with better oncologic quality.


Assuntos
Colo Transverso , Neoplasias do Colo , Laparoscopia , Colectomia , Humanos , Excisão de Linfonodo
4.
Drug Test Anal ; 14(6): 1065-1078, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35088572

RESUMO

In this work, 1-[(2″-fluorophenyl)(methylimino)methyl]cyclopentan-1-ol (2-fluorodeschlorohydroxylimine) was identified as a suspected chemical precursor of 2-fluorodeschloroketamine (2-FDCK) using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-quadrupole/time-of-flight mass spectrometry (GC-Q/TOF-MS) and comparing the data with those of ketamine and its chemical precursor, hydroxylimine. Furthermore, the entire fragmentation pathway of 2-fluorodeschlorohydroxylimine was theorized from the GC-MS spectrum recorded using an electron ionization (EI) source, and the mechanisms and decomposition pathways of 2-fluorodeschlorohydroxylimine were elucidated. In protic solvents, the nitrogen atom in the C═N group of 2-fluorodeschlorohydroxylimine underwent a protonation reaction. Thereafter, the traces of water present in protic solvents promoted the hydrolysis of the protonated imine, and a carbon cation was obtained following the loss of methylamine. The carbon cation could follow the classical decomposition mechanism of imines and yield an α-hydroxyl ketone, which was the major decomposition product, (2'-fluorophenyl)(1″-hydroxycyclopentyl)methanone. The cation could also undergo a loop expansion rearrangement and yield another α-hydroxyl ketone, 2-(2'-fluorophenyl)-2-hydroxycyclohexan-1-one. The structures of the two aforementioned decomposition products were elucidated using several techniques including theoretical calculation, GC-MS, nuclear magnetic resonance (NMR), the prediction and assistance elucidation functions of ACDLabs-Structure Elucidator Suite, and the virtual separation technology of diffusion-ordered spectroscopy. The aforementioned study revealed important information about the chemical precursor of 2-FDCK and its decomposition. Furthermore, a set of methods for the qualitative analysis of 2-fluorodeschlorohydroxylimine were established, which facilitated accurate analysis of 2-fluorodeschlorohydroxylimine samples following decomposition or destruction.


Assuntos
Carbono , Cetonas , Cromatografia Gasosa-Espectrometria de Massas/métodos , Solventes
5.
World J Gastroenterol ; 27(17): 1993-2014, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34007135

RESUMO

BACKGROUND: Previous studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIM: To investigate the role of TP73-AS1 in the growth and metastasis of PC. METHODS: The expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTS: The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSION: Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética
6.
Gastric Cancer ; 22(1): 48-59, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29748877

RESUMO

BACKGROUND: Podocalyxin-like 1 (PODXL) was reported to be closely associated with the development of various cancers, yet its functional roles and molecular mechanisms remain vague. The aim of our study was to investigate the clinical significance, biological function and molecular mechanism of PODXL in gastric cancer (GC). METHODS: The level of PODXL in GC tissues was detected applying GC tissues microarray, fresh GC tissues and public database (Oncomine). The invasion, metastasis and tumorigenesis role of PODXL were performed in vitro and in vivo. The correlations between KLF4 and PODXL was determined in GC tissues microarray and fresh GC tissues, and the molecular regulatory mechanism between KLF4 and PODXL was explored in vitro. RESULTS: The high level of PODXL was detected in GC tissues with advanced T stage, lymph node metastasis, Union for International Cancer Control stage and poor differentiation. And Cox proportional hazards model revealed that PODXL can serve as an independent prognostic indicator for disease-free survival and overall survival of GC patients. Moreover, downregulation of PODXL could inhibit EMT and reduce invasion and metastasis in vitro as well as tumorigenesis in vivo. Additionally, our findings showed that PODXL may be a significant downstream target of KLF4. CONCLUSIONS: KLF4/PODXL signaling pathway assumes an irreplaceable role in tumorigenesis, invasion and metastasis of human GC and PODXL serves as an independent prognostic indicator for GC patients.


Assuntos
Biomarcadores Tumorais/análise , Transição Epitelial-Mesenquimal/fisiologia , Fatores de Transcrição Kruppel-Like/metabolismo , Sialoglicoproteínas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Animais , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Fator 4 Semelhante a Kruppel , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade
7.
Int J Anal Chem ; 2018: 3104569, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30327671

RESUMO

A desktop NMR spectrometer was used to qualitatively analyze samples in drug-related cases in order to enhance the accuracy of the results and identify new drugs. Twelve known drugs and their derivatives were used to establish the parameters, conditions, and procedures for the methods and validate the feasibility and reliability of the methods. First, 1-D and 2-D NMR data for these 12 drugs and their derivatives were obtained in detail using a 600-MHz NMR spectrometer to create a data library. Next, some of these 12 drugs were analyzed using a Picospin 80 MHz desktop NMR spectrometer to set up the analytical procedure and method. With the procedure and method established, real case samples were analyzed and the data were compared to those obtained by a standard method. The results indicate that the desktop NMR spectrometer is a reliable and promising approach that can be used in criminology to quickly identify whether or not samples contain illegal drugs.

8.
Am J Transl Res ; 9(4): 1886-1895, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28469793

RESUMO

BACKGROUND: We previously showed that miR-301a-3p affects the invasion and migration abilities of pancreatic cancer cells. Here, we explore the role of miR-301a-3p in chemoresistance, which represents a major obstacle in cancer treatment. METHODS: We tested the effects of miR-301a-3p ongemcitabine resistance in cytotoxicity assays in vitro and in vivo. We used quantitative real-time PCR (qRT-PCR) to measure miR-301a-3p expression in wild-type and gemcitabine-resistant pancreatic cancer cells. We performed Western blot, qRT-PCR, and luciferase and rescue assays to confirm the direct target of miR-301a-3p. RESULTS: The overexpression and inhibition of miR-301a-3p promoted and reversed, respectively, gemcitabine resistance in pancreatic cancer cells in vitro. The role of miR-301-3p in chemoresistance was dependent on PTEN. The suppression of miR-301-3p expression sensitized pancreatic cancer cells to gemcitabine chemotherapy in a xenograft mouse model. CONCLUSION: MiR-301a-3p confers resistance to gemcitabine by regulating the expression of PTEN. The co-delivery of miR-301a-3p and gemcitabine might be an effective therapeutic regimen for patients with pancreatic cancer.

9.
Oncotarget ; 8(21): 34867-34883, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28432273

RESUMO

BACKGROUND: Our study aimed to investigate the clinicopathological feature and prognostic role of miR-509-3-5P in gastric cancer, to determine the invasive and metastatic role of miR-509-3-5P in vitro and in vivo and to explore the molecular mechanism between miR-509-3-5P and PODXL. RESULTS: Strikingly lower miR-509-3-5P expression was detected in gastric cancer tissues with advanced tumor stage, poor differentiation and advanced pT stage, and was regarded as an independent prognostic role for poor prognosis. MiR-509-3-5P expression was markedly down-regulated in gastric cancer cell lines and tissues comparing with normal gastric cell and adjacent normal tissues, respectively. Decreased expression of miR-509-3-5P promoted the colony, migration and invasion abilities of gastric cancer cells in vitro as well as tumorigenesis and lymph node metastasis in vivo. Based on the luciferase assay and tissue microarray, PODXL was regarded as a target gene of miR-509-3-5P. MATERIALS AND METHODS: The expression of miR-509-3-5P in gastric cancer patients and its clinicopathological relationships as well as prognostic role was studied employing tissue microarray; qRT-PCR was applied to explore miR-509-3-5P expression in gastric cancer cell lines and samples. Moreover, public database was used to analyze the expression of miR-509-3-5P and PODXL. Functional and molecular mechanism experiments were performed in vitro and in vivo. CONCLUSIONS: Overexpression of miR-509-3-5P inhibits the invasion and metastasis of gastric cancer in vitro and in vivo, functioning as a tumor suppressor, by targeting PODXL. More importantly, miR-509-3-5P was downregulated in gastric cancer tissues and may serve as a novel prognostic indicator for gastric cancer.


Assuntos
MicroRNAs/genética , Sialoglicoproteínas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Camundongos , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
10.
Cancer Lett ; 389: 11-22, 2017 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-28043911

RESUMO

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , MicroRNAs/fisiologia , Proteínas Monoméricas de Ligação ao GTP/fisiologia , Neoplasias Gástricas/etiologia , Proteínas Reguladoras de Apoptose , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
11.
Oncol Lett ; 12(4): 2381-2388, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27698803

RESUMO

The aim of the present study was to investigate the expression and functions of Forkhead box protein M1 (FoxM1), Caveolin-1 (Cav-1) and E-cadherin in colorectal cancer (CRC), and to determine the correlations among these proteins in CRC development and progression. The protein expression of FoxM1, Cav-1 and E-cadherin was identified using a human CRC and normal tissue microarray. A standard immunohistochemistry assay was performed employing anti-FoxM1, anti-Cav-1 and anti-E-cadherin antibodies. The clinicopathological significance of FoxM1, Cav-1 and E-cadherin in CRC was determined, and correlations were investigated between FoxM1 and Cav-1, FoxM1 and E-cadherin, Cav-1 and E-cadherin, respectively. The level of FoxM1, Cav-1 and E-Cadherin protein expression in CRC was found to be associated with pathological grade, tumor clinical stages and the presence of metastasis, respectively. Elevated expression of FoxM1 and Cav-1 was observed in the CRC tissues, and a significant correlation was found between the two proteins in CRC. However, it was also observed that FoxM1 was overexpressed while E-cadherin expression was low, indicating that there was a negative correlation between FoxM1 expression and E-cadherin expression. Moreover, there was also a negative correlation between Cav-1 and E-cadherin expression. Overall, the elevated expression of FoxM1 and Cav-1 in a human CRC microarray provided novel clinical evidence to elucidate the fact that they may play a critical role in the development and progression of CRC by negatively regulating E-cadherin expression. Furthermore, the positive correlation between FoxM1 and Cav-1 suggested that the proteins may constitute a novel signaling pathway in human CRC.

12.
Oncol Lett ; 12(4): 2445-2450, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27698811

RESUMO

The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques. In gastric cancer tissues, the expression of FoxM1 and E-cadherin was strongly positive, but it was weak in normal gastric mucosa. Overexpression of FoxM1 was evident in gastric cancer, and was associated with poor tumor differentiation (P<0.05), advanced tumor state (P<0.05) and lymph node (or distant) metastasis (P<0.05), whereas E-cadherin had the opposite effects. Furthermore, the correlation between FoxM1 and E-cadherin expression in gastric cancer tissue was negative. In conclusion, the high FoxM1 expression and low E-cadherin expression in gastric cancer tissue suggests that these proteins play a critical role in the development and progression of gastric cancer.

13.
Biochem Biophys Res Commun ; 478(1): 67-73, 2016 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-27453340

RESUMO

Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC.


Assuntos
Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Proteínas de Homeodomínio/genética , Reto/patologia , Idoso , Colo/metabolismo , Neoplasias Colorretais/diagnóstico , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reto/metabolismo , Análise de Sobrevida
14.
Se Pu ; 33(7): 691-8, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26672196

RESUMO

A new and sensitive analytical method has been developed for the simultaneous determination of seven anticoagulant rodenticides in whole blood and urine samples by liquid chromatography-linear ion trap mass spectrometry (LC-LIT/MS) with on-line solid phase extraction (on-line SPE). The samples were treated with acetonitrile, followed by dilution, centrifugation, and filtration. The resulting solution was injected into the LC system directly and processed by on-line SPE column for enrichment and purification. Separation was performed on a C18 column with mixed mobile phases of methanol and 0.02 mol/L ammonium acetate aqueous solution for gradient elution. The analytes were detected by the mass spectrometer with electrospray ionization (ESI) in negative mode. MS2 full scan signals of the target parent ions within the locked retention time window were recorded. Self-built database searching was performed for qualitative confirmation, and MS2 fragment ions with high sensitivity and specificity were selected for quantification. Simultaneous qualitative and quantitative analyses of the seven rodenticides were achieved in this way. Good linearities were obtained within the investigated mass concentration ranges of the seven rodenticides, with r2 ≥ 0.9958 in blood and r2 ≥ 0.9946 in urine. The LODs varied from 0.02 ng/mL to 1.00 ng/mL, and the LOQs varied from 0.10 ng/mL to 4.00 ng/mL. The recoveries at three spiked levels in blood and urine samples ranged from 81.0% to 113.9%, with RSDs of 0.1%-6.2% (n = 6). The developed method is simple, sensitive, and can be used for the rapid detection and accurate quantification of the seven anticoagulant rodenticides in whole blood and urine samples.


Assuntos
Rodenticidas/sangue , Rodenticidas/urina , Espectrometria de Massas por Ionização por Electrospray , Anticoagulantes/sangue , Anticoagulantes/urina , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Limite de Detecção , Sensibilidade e Especificidade , Extração em Fase Sólida
15.
Oncotarget ; 6(25): 21046-63, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26019136

RESUMO

BACKGROUND: Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. METHODS: By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. RESULTS: Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues. CONCLUSIONS: MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.


Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteína Smad4/metabolismo , Idoso , Animais , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Transplante de Neoplasias , Pancreaticoduodenectomia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Análise Serial de Tecidos
16.
Tumour Biol ; 36(1): 111-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25464861

RESUMO

Transforming growth factor-ß (TGF-ß) regulates cell functions and has key roles in pancreatic cancer development. SMAD4, as one of the Smads family of signal transducer from TGF-ß, mediates pancreatic cell proliferation and apoptosis and is specifically inactivated in half of advanced pancreatic cancers. In recent years, many advances concerning SMAD4 had tried to unravel the complex signaling mechanisms of TGF-ß and its dual role of tumor-suppressive and tumor-promoting efforts in pancreatic cancer initiation and progression through SMAD4-dependent TGF-ß signaling and SMAD4-independent TGF-ß signaling pathways. Meanwhile, its potential prognostic value based on immunohistochemical expression in surgical sample was variably reported by several studies and short of a systematic analysis. This review aimed to discuss the structure, functions, and regulation of this principal protein and its effects in determining the progression and prognosis of pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/metabolismo , Proteína Smad4/fisiologia , Animais , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Pancreáticas/patologia , Prognóstico , Transdução de Sinais , Fator de Crescimento Transformador beta/fisiologia
17.
World J Gastroenterol ; 21(48): 13532-41, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26730165

RESUMO

AIM: To assess the diverse immediate and long-term clinical outcomes, a retrospective comparison between laparoscopic and conventional operation was performed. METHODS: A total number of 916 clinical cases, from January 2006 to December 2013 in our hospital, were analyzed which covered 492 patients underwent the laparoscopy in radical resection (LRR) and 424 cases in open radical resection (ORR). A retrospective analysis was proceeded by comparing the general information, surgery performance, pathologic data, postoperative recovery and complications as well as long-term survival to investigate the diversity of immediate and long-term clinical outcomes of laparoscopic radical operation. RESULTS: There were no statistically significance differences between gender, age, height, weight, body mass index (BMI), tumor loci, tumor node metastasis stages, cell differentiation degree or American Society of Anesthesiologists scores of the patients (P > 0.05). In contrast to the ORR group, the LRR group experienced less operating time (P < 0.001), a lower blood loss (P < 0.001), and had a 2.44% probability of conversion to open surgery. Postoperative bowel function recovered more quickly, analgesic usage and the average hospital stay (P < 0.001) were reduced after LRR. Lymph node dissection during LRR appeared to be slightly more than in ORR (P = 0.338). There were no obvious differences in the lengths and margins (P = 0.182). And the occurrence rate in the two groups was similar (P = 0.081). Overall survival rate of ORR and LRR for 1, 3 and 5 years were 94.0% and 93.6% (P = 0.534), 78.1% and 80.9% (P = 0.284) and 75.2% and 77.0% (P = 0.416), respectively. CONCLUSION: Laparoscopy as a radical operation for rectal cancer was safe, produced better immediate outcomes. Long-term survival of laparoscopy revealed that it was similar to the open operation.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Retais/cirurgia , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
PLoS One ; 9(10): e108348, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25299478

RESUMO

AIMS: This study sought to evaluate the prognostic significance of postoperative complications for colon cancer patients undergoing laparoscopic surgery. METHODS: From May 2006 to May 2009, a total 224 patients who underwent laparoscopic curative resection (R0) for colon cancer were included in our retrospective study. Postoperative complications were evaluated according to a standardized grading system. The main outcome measurements of our study were overall survival (OS) and relapse-free survival (RFS), which were then compared between the no complication and complication groups. Univariate and multivariate analysis were used to assess the correlation between complications and prognosis. RESULTS: Fifty-nine postoperative complications occurred in 43 patients. The overall morbidity rate was 26.3%. The 5-year OS in the complication group was 41.4% compared with 78.5% in the no complication group (P<0.001). The cumulative incidence of relapse was also more aggressive in patients with complications (5-year RFS: complication group 40.9% vs. no complication group 82.1%, P<0.001). Multivariate analysis identified complications as a significant factor increasing the risk for both OS (RR 2.737; 95% CI 1.512-4.952; P = 0.001) and RFS (RR 4.247; 95% CI 2.291-7.876; P<0.001). CONCLUSION: Postoperative complications could pose a significant adverse impact not only on OS but also on RFS in patients with colon cancer even when laparoscopic R0 resection is available.


Assuntos
Colectomia/efeitos adversos , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Laparoscopia/efeitos adversos , Idoso , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/etiologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
19.
World J Surg Oncol ; 12: 184, 2014 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-24919472

RESUMO

BACKGROUND: The impact of obesity on surgical outcomes after laparoscopic colorectal cancer resection in Chinese patients is still unclear. METHODS: We retrospectively reviewed the prospectively collected data from 527 consecutive colorectal cancer patients who under went laparoscopic resection from January 2008 to September 2013. Patients were categorized into three groups: nonobese (body mass index (BMI) <25.0 kg/m2), obese I (BMI 25.0 = to 29.9 kg/m2) and obese II (BMI ≥30.0 kg/m2). Clinical characteristics, surgical outcomes and postoperative complications were compared between nonobese, obese I and obese II patients. RESULTS: From among the 527 patients, there were 371 patients with in the nonobese group, 142 patients in the obese I group and 14 patients in the obese II group. The patients were well-matched for age, sex and American Society of Anesthesiologists class, except for BMI (P = 0.001). The median operative time correlated highly significantly with increasing weight (median: nonobese = 135 minutes, obese I = 145 minutes, obese II = 162.5 minutes; P = 0.001). There appeared to be a slight tendency toward grade III complications (rated according to the Clavien-Dindo Classification of Surgical Complications) in the obese II group, but this difference was not significant (nonobese = 5.1%, obese I = 3.5% and obese II = 14.3%; P = 0.178). None of the grade III complications which occurred in the obese II group were wound dehiscences that required a stitch. Other aspects, such as estimated blood loss, harvested lymph nodes, operation type, pathological results, conversion rate and overall postoperative complications, were not statistically significant. CONCLUSION: With sufficient experience, laparoscopic colorectal cancer surgery is feasible and safe in obese Chinese patients.


Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia/efeitos adversos , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , China , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Obesidade/fisiopatologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
20.
Tumour Biol ; 35(8): 8115-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24840635

RESUMO

Using the uniform complication grading system to evaluate postoperative complications after laparoscopic colorectal surgery is the purpose of the present study. Surgical complications were defined as grades I, II, III, IV, and V recommended by Dindo et al. Patients were categorized into three pairs: complication group (CG) and non-complication group (NCG), minor complication group (MiCG, grades I-II) and non-minor complication group (NMiCG), and major complication group (MaCG, grades III-V) and non-major complication group (NMaCG); of the 570 patients, 431 patients were discharged with no complications, and 174 complications occurred in 119 patients. The percent of grades I, II, III, IV, and V complications were 4.7, 20, 4.7, 0.7, and 0.4 %, respectively. Complications were significantly associated with male gender, larger tumor volume, and more estimated blood loss (EBL). The multivariate analysis revealed that male and EBL ≥150 ml were found to be independent predictors of postoperative complications. In subgroup analysis, patients with larger tumor volume were at significantly higher risk of postoperative major complications, and male gender and EBL ≥150 ml remained independent predictors of developing minor postoperative complications. Patients with postoperative complications would significantly experience longer hospital stay, later fluid intake, and delayed urinary catheter removal. Male, larger tumor volume, and more EBL were significant risk factors for laparoscopic colorectomy.


Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Índice de Gravidade de Doença , Adulto , Idoso , Neoplasias Colorretais/patologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Fatores de Risco , Caracteres Sexuais , Carga Tumoral
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