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1.
Food Sci Nutr ; 9(10): 5379-5390, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34646509

RESUMO

To improve the antioxidant efficiency of mulberry leaf protein (MLP), alcalase, protamex, papain, flavourzyme, neutrase, and trypsin were used to hydrolyze MLP. The yield of soluble peptides, secondary structures, molecular weight distributions, and antioxidant activities of MLP hydrolysates (MLPHs) were investigated. Results showed that the native MLP was rich in the fraction above 6.5 kDa and was mainly composed of ß-sheets, while MLPHs were abundant in the fractions of 0.3-0.6 kDa and 0.6-6.5 kDa and were mainly composed of disordered coils and ß-folds. Limited hydrolysis of MLP could lead to better antioxidant activity than extensive hydrolysis. After enzymatic hydrolysis, the content of total sugar and total phenol in MLP increased significantly. MLP hydrolysates prepared with neutrase, alcalase, and protamex were preferable to other enzymes. Meanwhile, an enzyme to substrate level of 1% and a hydrolysis time of 2 hr were the optimum conditions to obtain higher antioxidant hydrolysates using neutrase.

3.
Biochem Genet ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34327615

RESUMO

The present study established a necroptosis model in vitro and investigated the role of HMGB1 in cell necroptosis. A combination of tumor necrosis factor-α and z-VAD-fmk was used to induce necroptosis in L929 cells with necroptosis inhibitor necrostatin-1 applied as an intervention. Flow cytometry and transmission electron microscopy (TEM) were used to measure cell necroptosis. Western blotting assay was applied to detect the expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3), mixed lineage kinase domain-like pseudokinase (MLKL) and HMGB1. Co-immunoprecipitation (Co-IP) assay was used to confirm the interaction between HMGB1 and RIPK3. Our study demonstrated that HMGB1 migrated from the nucleus to the cytoplasm at the onset of necroptosis and was subsequently released passively to the extracellular matrix. Further experiments determined that the binding of HMGB1 with RIPK3 in the cytoplasm was loose during necroptosis. By contrast, when necroptosis was inhibited, the interaction in the cytoplasm was tight suggesting that this association between HMGB1 and RIPK3 might affect its occurrence. In conclusion, the transfer of HMGB1 from nucleus to cytoplasm, and its interaction with RIPK3 might be potentially involved in necroptosis.

4.
Int J Gen Med ; 14: 2751-2761, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188529

RESUMO

Background: Accurate prediction of the survival of cutaneous melanoma (CM) permits the selection of the optimal treatment. Currently, the TNM stage has limitations in predicting the survival of CM. There is evidence that the WNT/ß-catenin signaling pathway has the potential to predict the CM prognosis. However, it still needs further investigation. Objective: This study aims to establish a nomogram incorporating the WNT/ß-catenin signaling pathway to improve the predicted accuracy of the overall survival (OS) of CM. Methods: Two hundred and eighty CM patients were recruited and followed up. The clinicopathological characteristics and the key genes of the WNT/ß-catenin signaling pathway (VEGF, ß-catenin, and DKK1) were chosen as potential variables associated with the OS. In the training cohort (n = 190), a nomogram was built to estimate the 1-, 3-, and 5-year OS, and its discriminations and calibrations were valid by the verification cohort (n = 90). The predicted accuracies of the nomogram with or without the Wnt/ß-catenin pathway and TNM stage were compared. Results: A nomogram integrating independent risk factors (ulceration, lymph node metastasis, distant metastasis, Breslow thickness, dermal mitoses, ß-catenin, VEGF, and DKK1), which were evaluated by a multivariate analysis, was constructed to predict the 1-, 3-, and 5-year OS of CM patients. Good discrimination and calibration were obtained regardless of the training or validation datasets. The nomogram incorporating the Wnt/ß-catenin signaling pathway showed the highest accuracy [area under the curve (AUC)=0.914, 0.852, 0.785] compared with the nomogram without the Wnt/ß-catenin signaling pathway (AUC=0.693, 0.640, 0.615) and the TNM stage (AUC=0.726, 0.693, 0.673). Conclusion: The prognostic value of the established nomogram incorporating the WNT/ß-catenin signaling pathway was better than it without WNT/ß-catenin signaling pathway and TNM stage, which might be beneficial in the development of optimal treatment options.

5.
Antioxidants (Basel) ; 10(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807689

RESUMO

In this study, blueberry and blackcurrant powder were chosen as the phenolic-rich enrichments for oat bran. A Rapid Visco Analyser was used to form blueberry and blackcurrant enriched oat pastes. An in vitro digestion process evaluated the changes of phenolic compounds and the in vitro antioxidant potential of extracts of pastes. The anthocyanidin profiles in the extracts were characterised by the pH differential method. The results showed that blueberry and blackcurrant powder significantly increased the content of phenolic compounds and the in vitro antioxidant capacity of pastes, while the total flavonoid content decreased after digestion compared to the undigested samples. Strong correlations between these bioactive compounds and antioxidant values were observed. Lipopolysaccharide-stimulated RAW264.7 macrophages were used to investigate the intracellular antioxidant activity of the extracts from the digested oat bran paste with 25% enrichment of blueberry or blackcurrant powder. The results indicated that the extracts of digested pastes prevented the macrophages from experiencing lipopolysaccharide (LPS)-stimulated intracellular reactive oxygen species accumulation, mainly by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway. These findings suggest that the bioactive ingredients from blueberry and blackcurrant powder enhanced the in vitro and intracellular antioxidant capacity of oat bran pastes, and these enriched pastes have the potential to be utilised in the development of the functional foods.

6.
Food Res Int ; 138(Pt A): 109756, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33292939

RESUMO

The α-amylase and α-glucosidase inhibitory activities by extracts of oat bran, blueberry and blackcurrant powders, as well as oat bran pastes supplemented 25% of blueberry and blackcurrant powder, were studied by measuring their half inhibitory (IC50) concentrations. Addition of blueberry or blackcurrant powder into oat bran paste increased α-amylase and α-glucosidase inhibitory activities with a decrease in IC50 values. The main anthocyanidin content was measured by pH differential method and the potential inhibitory mechanisms of these extracts were also investigated by detailed inhibition kinetics and docking simulations. The results showed that: (1) cyanidin and delphinidin were the main anthocyanidin profiles in extracts; (2) only blackcurrant powder was a competitive inhibitor, while other extracts were all mixed-type inhibitors against α-amylase; (3) both blueberry- and blackcurrant-enriched pastes were competitive inhibitors, while other extracts were all mixed-type inhibitors towards α-glucosidase; (4) the α-amylase and α-glucosidase inhibitory activities by extracts were potentially driven by hydrogen bonding, cyanidin-3-glucoside and delphinidin-3-glucoside had stronger binding affinity compared to malvidin-3-glucoside and cyanidin-3-rutinside. This study suggested supplementary of blueberry and blackcurrant with oat bran might be a potential source of bioactive products for antidiabetic activity.


Assuntos
Mirtilos Azuis (Planta) , Diabetes Mellitus Tipo 2 , Avena , Inibidores de Glicosídeo Hidrolases/farmacologia , Pós , alfa-Amilases , alfa-Glucosidases
7.
J Agric Food Chem ; 68(44): 12295-12309, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33095019

RESUMO

Garlic polysaccharides are great potential agents because of their anti-inflammation, antioxidation, and immunomodulation properties. However, few studies have reported their anti-inflammatory effects on improving the colon system and corresponding intestinal microbiota. Herein, a water-soluble garlic polysaccharide (WSGP) was extracted from Jinxiang garlic to evaluate its effects on ameliorating dextran sulfate sodium (DSS)-induced colitis in a mouse model. The results showed that (1) after administration of the WSGP (200 or 400 mg/kg/day), the feed intake, body weight, and colon length of colitic mice were increased, while the disease activity index and the histological score of colitic mice were decreased; (2) the WSGP reduced the colonic tissue damage and inhibited the expression of inflammatory factors (interleukin 6, interleukin 1 beta , and tumor necrosis factor alpha); and (3) the WSGP enhanced the production of short-chain fatty acids and improved the composition of intestinal microbiota. The key microorganisms, including Muribaculaceae, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Mucispirillum, Helicobacter, Ruminococcus_1, and Ruminiclostridium_5, were identified to be associated with inflammatory bowel diseases. Taken together, this study proved that WSGP supplementation could alleviate DSS-induced colitis by improving mucosal barriers, blocking proinflammatory cytokines, and modulating gut microbiota.


Assuntos
Anti-Inflamatórios/administração & dosagem , Colite/tratamento farmacológico , Colite/microbiologia , Alho/química , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Anti-Inflamatórios/química , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colite/induzido quimicamente , Colite/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Polissacarídeos/química
8.
9.
PLoS One ; 14(4): e0214822, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939162

RESUMO

Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of ß-catenin. Taken together, our data identified a miR-4524b-5p/WTX/ß-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , MicroRNAs/genética , Proteínas Supressoras de Tumor/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Transplante de Neoplasias , Proteínas Supressoras de Tumor/antagonistas & inibidores , Neoplasias do Colo do Útero/metabolismo
10.
Biochem Biophys Res Commun ; 496(2): 294-301, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29317206

RESUMO

This study aimed to explore the mechanism of impaired autophagy flux induced by exendin-4 and its role on cell apoptosis in pancreatic AR42J cells. The AR42J cells were treated with various concentration of exendin-4 for several time points to assess its cytotoxicity by MTT assay. Then the AR42J cells were treated by 10pM exendin-4 for 72 h, the cell death was analyzed by flow cytometry and caspase-3 level was examined by Western blot with or without the pretreatment of z-VAD-fmk to testify whether exendin-4 induces the cell apoptosis. The protein levels of LC3B, p62 and LAMP-2 were assessed by Western blot, the mRNA level of LAMP-2 was quantified by quantitative PCR in the absence or presence of LAMP-2 over-expression plasmid and the expression and activity of CatB and CatL were tested by ELISA or activity assay methods in AR42J cells treated by exendin-4. The normal rats and the diabetes-model rats by high-fat and high-sugar diet for two month then with streptozotocin intraperitoneally were subcutaneously injected with exendin-4 for 10 weeks to test the expression of LAMP-2 mRNA and protein in the pancreas. Cells pretreated with Bafilomycin A1 were detected for LC3B and p62 expressions by Western blot. Cells pretreated by 3-MA were used to assess whether 3-MA can protect from exendin-4 cytotoxicity. We found that exendin-4 can decrease the AR42J cell viability as well as increase the cell death and cleaved caspase-3 level, which all can be inhibited by z-VAD-fmk. Exendin-4 can downregulate the expression of LAMP-2 and then impair the autophagy flux to induce the accumulation of LC3B-II and p62, but cannot change the expression and activity of CatB and CatL. Bafilomycin A1 almostly have no impact on the change of LC3B and p62 protein levels induced by exendin-4. Both 3-MA and overexpressed LAMP-2 can reduce the cytotoxicity of exendin-4. Therefore, we considered the down-regulation of LAMP-2 which can impair the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes to induce the AR42J cell apoptosis as the potential mechanism of chronic pancreatitis induced by exendin-4.


Assuntos
Células Acinares/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/genética , Proteína 2 de Membrana Associada ao Lisossomo/genética , Peptídeos/toxicidade , Peçonhas/toxicidade , Células Acinares/citologia , Células Acinares/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Autofagia/genética , Caspase 3/genética , Caspase 3/metabolismo , Catepsina B/genética , Catepsina B/metabolismo , Catepsina L/genética , Catepsina L/metabolismo , Linhagem Celular , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica/efeitos adversos , Exenatida , Regulação da Expressão Gênica , Proteína 2 de Membrana Associada ao Lisossomo/antagonistas & inibidores , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Macrolídeos/farmacologia , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Ratos , Ratos Sprague-Dawley , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , Estreptozocina
11.
Pancreas ; 46(1): 83-88, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27518464

RESUMO

OBJECTIVES: The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. METHODS: Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. RESULTS: Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. CONCLUSIONS: Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.


Assuntos
Autofagia/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Peptídeos/farmacologia , Peçonhas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ácido Aspártico Proteases/metabolismo , Linhagem Celular , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipoglicemiantes/farmacologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismo
12.
Mol Med Rep ; 14(6): 5507-5513, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27878276

RESUMO

High-motility group box protein 1 (HMGB1) has an important role in autophagy; however, its exact role in acute necrotizing pancreatitis (ANP) remains unknown. The present study aimed to investigate the expression pattern of HMGB1 in ANP, and to determine its association with autophagy. Sprague Dawley rats (weight, 350±30 g, n=48) were randomly divided into control (n=12) and experimental (n=36) groups. Experimental rats were retrogradely injected with 5% sodium taurocholate into the biliopancreatic duct to induce ANP. Control rats received an equal amount of saline. Serum amylase levels were used to determine whether the model had been successfully generated. Autophagosomes in pancreatic acinar cells were observed under electron microscopy. The expression levels of HMGB1 and Beclin 1 were detected in pancreatic tissues by western blotting, quantitative polymerase chain reaction and immunohistochemistry. HMGB1 levels were also determined in the serum and in isolated nuclei. The results demonstrated that autophagy was detected at 3 h post­ANP induction; however, HMGB1 expression remained unaltered during the early stage (0­6 h; P>0.05). HMGB1 expression was significantly increased at 12 h, and was still increasing at 24 h (P<0.05). Notably, HMGB1 was increased in the nuclei compared with in the cytoplasm at 3­6 h. Furthermore, serum HMGB1 levels began to increase at 3 h, and reached the highest levels at 24 h in the ANP group. In conclusion, in an ANP model, HMGB1 was initially increased in the nuclei to initiate autophagy. Subsequently, it moved into the cytoplasm, where it interacted with Beclin 1 to enhance autophagy, and HMGB1 was released into the blood, leading to the deterioration of ANP.


Assuntos
Autofagia/genética , Expressão Gênica , Proteína HMGB1/genética , Pancreatite Necrosante Aguda/genética , Amilases/sangue , Animais , Proteína Beclina-1/sangue , Proteína Beclina-1/metabolismo , Biomarcadores , Modelos Animais de Doenças , Proteína HMGB1/sangue , Proteína HMGB1/metabolismo , Imuno-Histoquímica , Masculino , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/ultraestrutura , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/metabolismo , Ratos
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(2): 232-237, 2016 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-28219869

RESUMO

OBJECTIVE: To explore the effects of silencing HERC4 on the proliferation, apoptosis, and migration of cervical cancer cell line Hela and the possible molecular mechanisms. METHODS: Three HERC4-specific small interfering RNAs (siRNAs) were transfected into Hela cells, and HERC4 expression in the cells was examined with Western blotting. CCK-8 assay, annexin V-FITC/PI assay, and wound healing assay were used to assess the effect of HERC4 silencing on the proliferation, apoptosis and migration ability of Hela cells. The expression levels of cyclin D1 and Bcl-2 in the cells were detected using Western blotting. RESULTS: Transfection of siRNA-3 resulted in significantly decreased HERC4 protein expression (P<0.01). HERC4 silencing by siRNA-3 markedly suppressed the proliferation and migration of Hela cells, increased the apoptosis rate (P<0.01) and reduced the expression levels of cyclin D1 and Bcl-2 (P<0.01). CONCLUSION: Silencing of HERC4 efficiently inhibits the proliferation, migration, and invasion of Hela cells in vitro, and the underlying mechanisms may involve the down-regulation of cyclin D1 and Bcl-2.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Interferência de RNA , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Regulação para Baixo , Feminino , Células HeLa , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , Transfecção , Ubiquitina-Proteína Ligases/genética , Neoplasias do Colo do Útero/patologia
14.
Zhongguo Zhong Yao Za Zhi ; 39(1): 34-9, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24754164

RESUMO

OBJECTIVE: In order to get the method for improving the salt resistance of Lycium ruthenium seeds and seedlings under NaCl stress, the seed germination and physiological characteristics of L. ruthenium seedlings was studied. METHOD: Several physiological indexes of L. ruthenium seeds under NaCl stress, such as the germination rate (Gr), germination vigor (Gv), germination index (Gi), vigor index (Vi), and relative salt damage rate were measured. Other indexes of the seedlings like relative water contents (RWC) , chlorophyll contents, soluble protein contents, electrolyte leakage, the contents of malondialdehyde (MDA), and peroxidase (POD) were also measured. RESULT: NaCl at lower concentration could promote the seed germination but inhibit the seed germination at higher concentration. After the treatment by CaCl2 at the different concentrations, all germination indexes were increased. With the increase of salt concentration, the relative water contents and the contents of chlorophyll were decreased, the content of MDA and electrolyte leakage were increased. The change trend of POD activity showed the first increase and then decrease with the increase of salt concentration, which was similar to that of the soluble protein. After the treatment by CaCl2, relative water contents, chlorophyll and POD activities were decreased more slowly, and also electrolyte leakage and MDA contents increased slowly. CONCLUSION: The CaCl2 could significantly alleviate the damages to the seeds and seedlings of L. ruthenium under NaCl stress, and promote the salt resistance to the seeds and seedlings of L. ruthenium.


Assuntos
Cálcio/farmacologia , Germinação/efeitos dos fármacos , Lycium/efeitos dos fármacos , Plântula/efeitos dos fármacos , Sementes/efeitos dos fármacos , Lycium/metabolismo , Lycium/fisiologia , Plântula/metabolismo , Plântula/fisiologia , Sementes/metabolismo , Sementes/fisiologia , Cloreto de Sódio/metabolismo
15.
Int J Gynecol Cancer ; 24(1): 149-55, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24362720

RESUMO

OBJECTIVE: This study aimed to identify prognostic factors of survival and improve treatment strategies in women diagnosed with primary malignant melanoma of the vagina. METHODS: Between December 2002 and August 2011, 44 patients with lesions confined to the vagina and diagnosed with melanoma at Fudan University Shanghai Cancer Center were evaluated retrospectively. Prognostic factors were analyzed by Kaplan-Meier method. RESULTS: With a median follow-up time of 18.9 months (range, 6.0-94.3 months), 30 (68.2%) patients developed recurrences, whereas 21 (47.7%) died of disease. Median progression-free survival (PFS) was 14.4 months and median overall survival (OS) was 39.5 months. Depth of invasion (DOI) was significantly associated with OS (P = 0.023), and there was an obvious tendency toward improved OS with a negative lymph node status (P = 0.063). The DOI was significantly associated with lymph node status (P = 0.047). The extent of surgery (wide local excision vs radical excision) was not associated with differences in PFS or OS (P = 0.573 and P = 0.842, respectively). Longer PFS was observed in patients who received adjuvant chemotherapy and radiotherapy (P = 0.038). CONCLUSIONS: The prognosis of primary vaginal melanoma is dependent on the DOI and lymph node status in our study. Surgical resection of disease, especially wide local excision, should be considered as the optimal treatment when complete removal of tumor with a negative margin is possible. Adjuvant therapy may be associated with a longer PFS.


Assuntos
Melanoma/mortalidade , Neoplasias Vaginais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Vagina/patologia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/terapia , Adulto Jovem
16.
Exp Cell Res ; 320(1): 12-20, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24183997

RESUMO

MicroRNAs(miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, but their involvement in the chemoresistance of human cervical squamous cell carcinoma is not fully understood. We found miR-181a was significantly up-regulated in specimens from patients with chemoresistant cervical squamous cell carcinoma. In this study, we aimed to clarify the role of miR-181a in regulating the chemoresistance of cervical cancer. Two human cervical squamous cancer cell lines, SiHa and Me180, were used. Enforced expression of miR-181a enhanced chemoresistance to cisplatin in cervical cancer cells through apoptosis reversion. In a nude mouse xenograft model, the overexpression of miR-181a markedly inhibited the therapeutic response to cisplatin. PRKCD, a target gene of miR-181a and a promoter of apoptosis, was negatively regulated by miR-181a. We found that the effect of miR-181a on chemoresistance was mediated by PRKCD. Additionally, silencing of PRKCD yielded an effect similar to that of miR-181a up-regulation and inhibited apoptosis in cervical cancer cells. Our findings suggest that miR-181a may function as an oncogene and induce chemoresistance in cervical squamous cell carcinoma cells at least in part by down-regulating PRKCD, thus may provide a biomarker for predicting chemosensitivity to cisplatin in patients with cervical squamous cancer.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Proteína Quinase C-delta/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/uso terapêutico , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteína Quinase C-delta/genética , Reação em Cadeia da Polimerase em Tempo Real , Relação Estrutura-Atividade , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
17.
Zhong Yao Cai ; 36(7): 1039-43, 2013 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-24417133

RESUMO

OBJECTIVE: To improve salt resistance of Codonopsis pilosula seeds and seedlings under different salt-alkaline stress, the seed germination and physiological characteristics of seedlings were studied. METHODS: Several physiological indexes of Codonopsis pilosula under different salt-alkaline stress were measured, such as the germination vigor, germination rate, relative germination rate and recovery germination rate,as well as others indexes like the contents of chlorophyll, soluble protein, water and MDA and the activities of POD and SOD. RESULTS: The inhibitory effects of three salts on seed germination were Na2 CO3 > NaCl + Na2 CO3 > NaCl with an increased salt concentration. The contents of chlorophyll, soluble protein and water were found significant different (P < 0.05) from the negative control group, along with the decreased of these indexes. However, positive correlation existed between MDA content and salt treatment concentration. In addition, the change trend of SOD and POD activity were similar. They were increased firstly, and then decreased as the stress intensity extended. CONCLUSION: The seeds and seedlings under different salt-alkaline stress were inhibited, with different inhibitory extent as Na2CO3 > NaCl + Na2 CO3 > NaCl.


Assuntos
Álcalis/metabolismo , Codonopsis/metabolismo , Sementes/crescimento & desenvolvimento , Cloreto de Sódio/metabolismo , Clorofila/metabolismo , Codonopsis/crescimento & desenvolvimento , Codonopsis/fisiologia , Germinação/fisiologia , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Plântula/fisiologia , Sementes/metabolismo , Sementes/fisiologia , Estresse Fisiológico , Sulfatos/metabolismo , Superóxido Dismutase/metabolismo
18.
Eur J Obstet Gynecol Reprod Biol ; 165(2): 307-12, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22938817

RESUMO

OBJECTIVE: Despite evidence that oestrogen may play an important role in the carcinogenesis of cervical cancer, its action and mechanism in cervical cancer invasion are not well defined. STUDY DESIGN: The invasion induced by 17ß-oestradiol (E2) was measured by invasion assay. Real-time polymerase chain reaction (PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and gelatin zymography were used to study the role of E2 on metastasis-related proteases. The signal pathway was also investigated. RESULTS: E2 was found to significantly enhance the invasion of cervical cell lines including HeLa, CaSki and SiHa cells, but not C33A cells. Moreover, E2 10(-8)M increased the expression and activation of matrix metalloproteinases (MMP-2 and MMP-9) in HeLa and CaSki cells, as shown by real-time PCR, Western blot, ELISA and gelatin zymography. The expression of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) was decreased significantly by E2. Pretreatment with GM6001 10 µM (total MMP inhibitor) or SB-3CT 20 µM (specific gelatinase inhibitor) blocked the pro-invasive effect of E2. E2 was found to induce invasion via the phosphatidylinositol 3-kinase (PI3K) signalling pathway. CONCLUSION: E2 may contribute to cervical cancer metastasis through activation of proteolysis and increased invasion via the PI3K pathway.


Assuntos
Estradiol/farmacologia , Invasividade Neoplásica/fisiopatologia , Metástase Neoplásica/fisiopatologia , Fosfatidilinositol 3-Quinases/fisiologia , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Proteólise/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Neoplasias do Colo do Útero/metabolismo
19.
Zhongguo Zhong Yao Za Zhi ; 37(20): 3036-40, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23311149

RESUMO

OBJECTIVE: In order to get the method for improving the salt resistance of Hedysarum polybotrys seeds and seedlings under different salt-alkaline stress, the seed germination and physiological characteristics of H. polybotrys seedlings were studied. METHOD: Several physiological indexes of H. polybotrys seeds under different salt-alkaline stress, such as the germination vigor, germination rate, relative germination rate, relative salt damage rate were measured. And others indexes of the seedlings like chlorophyll contents, soluble protein contents, the permeability of plasmalemma, the activities of POD and SOD were also measured. RESULT: Different salt-alkaline stress decreased the germination rate, vigor of germinate, germination index, while relative salt damage rate increased. With the increased salt-alkaline concentration, the adverse effects became more obvious. The strength of the salts: Na2CO3 > Na2SO4 > NaCl. With the increase of the salt-alkaline concentration, the chlorophyll contents and the soluble protein contents decreased, but the permeability of plasmalemma increased. The change trend of SOD and POD activity was similar, it is increased firstly, and then decreased as the stress intensity extended, the most significant increase of Na2SO4 and Na2CO3 in the concentration of salt-alkaline was 25 mmol x L(-1), but NaCl was 50 mmol x L(-1). CONCLUSION: The seeds and seedlings inhibition of the salts was Na2CO3 > Na2SO4 > NaCl.


Assuntos
Álcalis/metabolismo , Fabaceae/metabolismo , Sementes/crescimento & desenvolvimento , Cloreto de Sódio/metabolismo , Fabaceae/crescimento & desenvolvimento , Fabaceae/fisiologia , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Plântula/fisiologia , Sementes/metabolismo , Sementes/fisiologia , Estresse Fisiológico
20.
Int J Gynecol Cancer ; 22(2): 186-90, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22146765

RESUMO

OBJECTIVE: To evaluate the incidence and the effective treatment of postoperative chylous ascites in patients with gynecologic malignancies. METHODS: In this report, we retrospectively reviewed the cases of 4119 patients who underwent pelvic and/or para-aortic lymph node dissection for gynecologic malignancies in Fudan University Cancer Hospital. RESULTS: Among these 4119 cases, 7 (0.17%) patients had chylous ascites postoperatively. The average age of these patients was 52 years. The mean time interval between operation and the appearance of chylous ascites was 30 days (range, 5-75 days). The incidence of chylous ascites after para-aortic lymphadenectomy was approximately 0.32% (5/1540), whereas the rate after pelvic lymphadenectomy alone was 0.077% (2/2579). All cases with chylous ascites were resolved by conservative treatment. This included placement of a peritoneal drainage tube. The mean time to resolution was 13 days (range, 2-28 days). None of the cases had recurrent chylous ascites during follow-up. CONCLUSIONS: Para-aortic lymph node dissection may be associated with postoperative chylous ascites. Patients may have their chylous ascites successfully treated with conservative management. An abdominal drainage tube can be a simple and effective approach and should be considered in the treatment.


Assuntos
Ascite Quilosa/epidemiologia , Neoplasias dos Genitais Femininos/cirurgia , Excisão de Linfonodo/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Aorta Torácica , China/epidemiologia , Ascite Quilosa/etiologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Admissão do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Veia Cava Inferior
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