Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
J Cancer Res Clin Oncol ; 150(2): 78, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316655

RESUMO

PURPOSE: Bone metastasis is a significant contributor to morbidity and mortality in advanced prostate cancer, and early diagnosis is challenging due to its insidious onset. The use of machine learning to obtain prognostic information from pathological images has been highlighted. However, there is a limited understanding of the potential of early prediction of bone metastasis through the feature combination method from various sources. This study presents a method of integrating multimodal data to enhance the feasibility of early diagnosis of bone metastasis in prostate cancer. METHODS AND MATERIALS: Overall, 211 patients diagnosed with prostate cancer (PCa) at Gansu Provincial Hospital between January 2017 and February 2023 were included in this study. The patients were randomized (8:2) into a training group (n = 169) and a validation group (n = 42). The region of interest (ROI) were segmented from the three magnetic resonance imaging (MRI) sequences (T2WI, DWI, and ADC), and pathological features were extracted from tissue sections (hematoxylin and eosin [H&E] staining, 10 × 20). A deep learning (DL) model using ResNet 50 was employed to extract deep transfer learning (DTL) features. The least absolute shrinkage and selection operator (LASSO) regression method was utilized for feature selection, feature construction, and reducing feature dimensions. Different machine learning classifiers were used to build predictive models. The performance of the models was evaluated using receiver operating characteristic curves. The net clinical benefit was assessed using decision curve analysis (DCA). The goodness of fit was evaluated using calibration curves. A joint model nomogram was eventually developed by combining clinically independent risk factors. RESULTS: The best prediction models based on DTL and pathomics features showed area under the curve (AUC) values of 0.89 (95% confidence interval [CI], 0.799-0.989) and 0.85 (95% CI, 0.714-0.989), respectively. The AUC for the best prediction model based on radiomics features and combining radiomics features, DTL features, and pathomics features were 0.86 (95% CI, 0.735-0.979) and 0.93 (95% CI, 0.854-1.000), respectively. Based on DCA and calibration curves, the model demonstrated good net clinical benefit and fit. CONCLUSION: Multimodal radiomics and pathomics serve as valuable predictors of the risk of bone metastases in patients with primary PCa.


Assuntos
Neoplasias Ósseas , Aprendizado Profundo , Neoplasias da Próstata , Masculino , Humanos , Radiômica , Imageamento por Ressonância Magnética , Neoplasias Ósseas/diagnóstico por imagem , Algoritmos , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos
2.
Redox Biol ; 69: 103026, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184996

RESUMO

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.


Assuntos
Betaína , Disfunção Cognitiva , Animais , Ratos , Ratos Sprague-Dawley , Betaína/farmacologia , Piroptose , Interleucina-18 , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Caspase 1 , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Homocisteína , Interleucina-1beta , Inflamassomos
3.
Neurochirurgie ; 70(1): 101515, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38052154

RESUMO

BACKGROUND: Transsphenoidal surgeons should try to avoid internal carotid artery (ICA) injury but also be prepared to manage it. We analyzed our experience with ICA injury during endoscopic transsphenoidal pituitary surgery and present associated risk factors and a management protocol. METHODS: We retrospectively reviewed and analyzed the medical records of 1596 patients who underwent endoscopic transsphenoidal surgery for pituitary tumor resection in our institution from January 2009 to October 2022. RESULTS: Six patients experienced an ICA injury. All received timely and effective hemostasis with immediate direct tamponade followed by endovascular treatment. No serious postoperative complications occurred. CONCLUSIONS: We proposed a treatment plan for ICA injuries encountered during endoscopic transsphenoidal surgery and described our hemostasis process, methods of endovascular treatment, and means of postoperative follow-up in detail.


Assuntos
Lesões das Artérias Carótidas , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Artéria Carótida Interna/cirurgia , Estudos Retrospectivos , Endoscopia/efeitos adversos , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/cirurgia
4.
CNS Neurosci Ther ; 30(3): e14140, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-36892036

RESUMO

AIMS: FoxO1 is an important target in the treatment of Alzheimer's disease (AD). However, FoxO1-specific agonists and their effects on AD have not yet been reported. This study aimed to identify small molecules that upregulate the activity of FoxO1 to attenuate the symptoms of AD. METHODS: FoxO1 agonists were identified by in silico screening and molecular dynamics simulation. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to assess protein and gene expression levels of P21, BIM, and PPARγ downstream of FoxO1 in SH-SY5Y cells, respectively. Western blotting and enzyme-linked immunoassays were performed to explore the effect of FoxO1 agonists on APP metabolism. RESULTS: N-(3-methylisothiazol-5-yl)-2-(2-oxobenzo[d]oxazol-3(2H)-yl) acetamide (compound D) had the highest affinity for FoxO1. Compound D activated FoxO1 and regulated the expression of its downstream target genes, P21, BIM, and PPARγ. In SH-SY5Y cells treated with compound D, BACE1 expression levels were downregulated, and the levels of Aß1-40 and Aß1-42 were also reduced. CONCLUSIONS: We present a novel small-molecule FoxO1 agonist with good anti-AD effects. This study highlights a promising strategy for new drug discovery for AD.


Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Regulação para Baixo , PPAR gama/genética
5.
Neurosurg Rev ; 46(1): 31, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36595070

RESUMO

Skull base tumors are challenging to treat because of their deep location, complex anatomy, and close proximity to important blood vessels and nerves. Furthermore, some patients with cranial tumors are found to have aneurysms, but there is no consensus on how to evaluate the impact of aneurysms on surgery and how to handle the lesions safely and effectively. We retrospectively reviewed our database to identify all patients with a skull base tumor treated in the Department of Neurosurgery of Beijing Tiantan Hospital affiliated with Capital Medical University from 2019 to 2021. The records of patients with skull base tumors associated with aneurysms were analyzed. The operative methods and postoperative follow-up information were collected. We analyzed a total of 481 patients with skull base tumors, comprising 224 males and 257 females with a mean age of 48 ± 14 years. Twenty-four patients (24/481, 5.0%) were diagnosed with aneurysms. For eight patients, it was considered necessary to perform aneurysm treatment before or during the tumor resection surgery. For the other 16 patients, the recommendation was to monitor the aneurysm or perform elective aneurysm treatment after tumor resection. All patients with both skull base tumors and aneurysms benefited from treatment. No severe postoperative complications occurred. We summarized the final treatment plan for all patients with skull base tumors with aneurysms and proposed a protocol to decrease the surgical risk of patients with skull base tumors associated with aneurysms.


Assuntos
Aneurisma , Neoplasias da Base do Crânio , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias da Base do Crânio/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Base do Crânio/cirurgia
6.
Antioxidants (Basel) ; 11(9)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36139729

RESUMO

Kombucha beverage is commonly prepared by black tea infusion fermentation without tea residues, and possesses various health benefits. In this paper, kombucha beverages of two non-Camellia sinensis teas, including vine tea (Ampelopsisgrossedentata) and sweet tea (Rubus suavissimus), were studied for the first time. The antioxidant activities and polyphenol contents of kombucha beverages were evaluated by ferric-reducing antioxidant power assay, Trolox equivalent antioxidant capacity assay, and Folin-Ciocalteu method, respectively. In addition, effects of tea residues on antioxidant capacities of kombucha beverages were evaluated. The results showed that kombucha beverages from vine tea and sweet tea possessed strong antioxidant activities (especially vine tea kombucha), and fermentation with tea residues could significantly increase antioxidant capacities (maximum increase of 38%) and total phenolic content (maximum increase of 55%) of two kombucha beverages compared with those without tea residues. Moreover, the sensory evaluations showed that the sensory evaluation scores of kombucha with tea residues could be improved compared with those without tea residues. Furthermore, the concentrations of several bioactive components in the kombucha beverages were detected by high-performance liquid chromatography. These kombucha beverages could be used for prevention of several diseases with related of oxidative stress.

7.
Foods ; 11(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36140883

RESUMO

Grape (Vitis vinifera L.) is one of the most popular fruits worldwide. It contains various bioactive compounds, such as proanthocyanidins, anthocyanins, flavonols, phenolic acids and stilbenes, the contents of which could vary considerably in grape skin, pulp and seed. Many studies have revealed that grape possesses a variety of health benefits, such as antioxidant, anti-inflammatory, gut-microbiota-modulating, anticancer and cardioprotective effects. Grape is eaten as fresh fruit and is also used as raw material to produce various products, such as wine, grape juice and raisins. Moreover, the byproducts of grape, such as grape pomace and grape seed, have many applications in the food industry. In this paper, the bioactive compounds in grape are briefly summarized based on literature published in recent years. In addition, the health benefits of grape and its bioactive components are discussed, with special attention paid to the underlying mechanisms. Furthermore, the applications of grape in the food industry are elucidated, especially the applications of grape pomace and grape seed. This paper can contribute to understanding the health benefits and mechanisms of grape and its bioactive compounds, as well as the promotion of the use of grape in the food industry.

8.
Foods ; 11(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36140990

RESUMO

The gut microbiota and their metabolites could play an important role in health and diseases of human beings. Short-chain fatty acids (SCFAs) are mainly produced by gut microbiome fermentation of dietary fiber and could also be produced by bacteria of the skin and vagina. Acetate, propionate, and butyrate are three major SCFAs, and their bioactivities have been widely studied. The SCFAs have many health benefits, such as anti-inflammatory, immunoregulatory, anti-obesity, anti-diabetes, anticancer, cardiovascular protective, hepatoprotective, and neuroprotective activities. This paper summarizes health benefits and side effects of SCFAs with a special attention paid to the mechanisms of action. This paper provides better support for people eating dietary fiber as well as ways for dietary fiber to be developed into functional food to prevent diseases.

9.
Antioxidants (Basel) ; 11(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36009200

RESUMO

Cancer is the leading cause of death in the world. Curcumin is the main ingredient in turmeric (Curcuma longa L.), and is widely used in the food industry. It shows anticancer properties on different types of cancers, and the underlying mechanisms of action include inhibiting cell proliferation, suppressing invasion and migration, promoting cell apoptosis, inducing autophagy, decreasing cancer stemness, increasing reactive oxygen species production, reducing inflammation, triggering ferroptosis, regulating gut microbiota, and adjuvant therapy. In addition, the anticancer action of curcumin is demonstrated in clinical trials. Moreover, the poor water solubility and low bioavailability of curcumin can be improved by a variety of nanotechnologies, which will promote its clinical effects. Furthermore, although curcumin shows some adverse effects, such as diarrhea and nausea, it is generally safe and tolerable. This paper is an updated review of the prevention and management of cancers by curcumin with a special attention to its mechanisms of action.

10.
Molecules ; 27(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889396

RESUMO

Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial activities. In addition, berberine shows anticancer effects on a variety of cancers, such as breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. The underlying mechanisms of action include inhibiting cancer cell proliferation, suppressing metastasis, inducing apoptosis, activating autophagy, regulating gut microbiota, and improving the effects of anticancer drugs. This paper summarizes effectiveness and mechanisms of berberine on different cancers and highlights the mechanisms of action. In addition, the nanotechnologies to improve bioavailability of berberine are included. Moreover, the side effects of berberine are also discussed. This paper is helpful for the prevention and treatment of cancers using berberine.


Assuntos
Antineoplásicos , Berberina , Microbioma Gastrointestinal , Plantas Medicinais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Humanos , Masculino , Obesidade/tratamento farmacológico
12.
J Pathol ; 257(5): 620-634, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35394061

RESUMO

Treatment of schwannomas in patients with neurofibromatosis type 2 (NF2) is extremely unsatisfactory, and innovative therapeutic approaches are urgently needed. However, the lack of clinically relevant NF2-associated schwannoma models has severely hampered drug discovery in this rare disease. Here we report the first establishment and characterization of patient-derived xenograft (PDX) and cell line models of NF2-associated schwannoma, which recapitulates the morphological and histopathological features of patient tumors, retain patient NF2 mutations, and maintain gene expression profiles resembling patient tumor profiles with the preservation of multiple key signaling pathways commonly dysregulated in human schwannomas. Using gene expression profiling, we identified elevated PI3K/AKT/mTOR networks in human NF2-associated vestibular schwannomas. Using high-throughput screening of 157 inhibitors targeting the PI3K/AKT/mTOR pathways in vitro, we identified a dozen inhibitors (such as BEZ235, LY2090314, and AZD8055) with significant growth-suppressive effects. Interestingly, we observed that three cell lines displayed differential therapeutic responses to PI3K/AKT/mTOR inhibitors. Furthermore, we demonstrated that two orally bioavailable inhibitors, AZD8055 and PQR309, suppressed NF2-associated schwannoma growth both in vitro and in vivo. In conclusion, our novel patient-derived models of NF2-associated schwannoma closely mimic the phenotypes and genotypes of patient tumors, making them reliable preclinical tools for testing novel personalized therapies. © 2022 The Pathological Society of Great Britain and Ireland.


Assuntos
Neurilemoma , Neurofibromatose 2 , Linhagem Celular , Xenoenxertos , Humanos , Neurilemoma/tratamento farmacológico , Neurilemoma/genética , Neurofibromatose 2/tratamento farmacológico , Neurofibromatose 2/genética , Neurofibromatose 2/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética
13.
Fitoterapia ; 145: 104573, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32222428

RESUMO

Three undescribed azaphilones, phomopsones A-C (1-3) and two known azaphilones (4-5) were isolated from the culture of endophytic fungus Phomopsis sp. CGMCC No.5416 from the stems of Achyranthes bidentata. Their structures were determined by spectroscopic analysis (HRESIMS, 1D and 2D NMR), and the absolute configurations were determined by CD spectroscopy. Compounds 2 and 3 showed significant inhibitory activities against HIV-1 with against HIV-1 with IC50 values of 7.6 and 0.5 µmol/L, respectively. Compounds 2 and 3 also displayed moderate cytotoxicity with CC50 values of 3.2-303 µmol/L against A549, MDA-MB-231 and PANC-1 cell lines. Moreover, compound 3 can induce the early apoptosis of PANC-1 cancer cells with the apoptosis rate of 28.54%.


Assuntos
Fármacos Anti-HIV/farmacologia , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Phomopsis/química , Pigmentos Biológicos/farmacologia , Achyranthes/microbiologia , Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos/isolamento & purificação , Apoptose , Benzopiranos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , China , Endófitos/química , HIV-1/efeitos dos fármacos , Humanos , Estrutura Molecular , Pigmentos Biológicos/isolamento & purificação , Caules de Planta/microbiologia
14.
Chin Med J (Engl) ; 132(7): 798-804, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30897594

RESUMO

BACKGROUND: The endoscopic transnasal approach has been proven to have advantages on the removal of the tumors in pterygopalatine fossa (PPF) and infratemporal fossa (ITF). Herein, this study aimed to describe a modified approach for resection of the tumors in these areas, both in cadaveric specimen and clinical patients. METHODS: The 20 adult cadaveric specimens and five patients with tumors in PPF and ITF were enrolled in this study. For the cadaveric specimens, ten were simulated anterior transmaxillary approach and ten were performed modified endoscopic transnasal transmaxillary approach. The exposure areas were compared between two groups and main anatomic structure were measured. Surgery was operated in the five patients with tumors of PPF and ITF to verify the experience from the anatomy. Perioperative management, intraoperative findings and postoperative complications were recorded and analyzed. RESULTS: The modified endoscopic transnasal transmaxillary approach provided as enough surgical exposure and high operability to the PPF and ITF as the anterior transmaxillary approach did. The diameter of maxillary artery in the PPF was 3.77 ±â€Š0.78 mm (range: 2.06-4.82 mm), the diameter of middle meningeal artery in the ITF was 2.79 ±â€Š0.61 mm (range: 1.54-3.78 mm). Four patients who suffered schwannoma got total removal and one of adenocystic carcinoma got subtotal removal. The main complications were facial numbness and pericoronitis of the wisdom tooth. No permanent complication was found. CONCLUSIONS: With the widespread use of neuroendoscopy, the modified endoscopic transnasal transmaxillary approach is feasible and effective for the resection of tumors located in PPF and ITF, which has significant advantages on less trauma and complications to the patients.


Assuntos
Neoplasias Infratentoriais/patologia , Fossa Pterigopalatina/patologia , Adulto , Feminino , Humanos , Neoplasias Infratentoriais/cirurgia , Masculino , Pessoa de Meia-Idade , Neuroendoscopia , Assistência Perioperatória , Complicações Pós-Operatórias , Fossa Pterigopalatina/cirurgia
15.
Phytomedicine ; 53: 18-27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668397

RESUMO

BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide. Cisplatin-based chemotherapy is the standard treatment for lung cancer, but chemoresistance and adverse effects especially cardiotoxicity limit its efficacy. PURPOSE: The efficacy of combination treatment of dendrobine, a plant alkaloid isolated from Dendrobium nobile, with cisplatin was examined as a possible anti-non-small cell lung cancer strategy. METHODS: The cytotoxicity of dendrobine and cisplatin against A549 lung cancer cells was analyzed by MTT and colony formation assays. Apoptosis was measured by annexin V/PI double staining. Apoptosis-related proteins were assessed by western blotting and qPCR analysis. In vivo efficacy was determined using A549 xenograft in nude mice. JNK and Bim inhibition were achieved by siRNA knockdown and/or chemical inhibition. Cardiotoxicity was assessed by serum creatine phosphokinase activity assay. RESULTS: Dendrobine induced apoptotic cell death through mitochondrial-mediated pathway. Combination treatment of dendrobine with cisplatin showed enhanced cytotoxicity through stimulation of JNK/p38 stress signaling pathways and, consequently, the induction of apoptosis involving pro-apoptotic proteins Bax and Bim. In addition, dendrobine attenuated the body weight reduction and cardiotoxicity induced by cisplatin in nude mice. CONCLUSION: The combination treatment showed enhanced anticancer activity toward non-small cell lung cancer cells without aggravating the cardiotoxic effects of cisplatin suggesting that the combination strategy deserves further investigation for human lung cancer treatment.


Assuntos
Alcaloides/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células A549 , Alcaloides/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Peso Corporal/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Agric Food Chem ; 66(27): 7054-7064, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29920075

RESUMO

Worldwide, colorectal cancer (CRC) is a deleterious disease causing millions of death annually. 5-Fluorouracil (5-FU) is a first-line chemotherapy for CRC, but chemoresistance and gastrointestinal mucositis limit its efficacy. Polyphenol-rich foods are increasingly popular due to their potential beneficial roles in preventing and treating cancer. Ellagitannins are a group of phenolic compounds commonly found in pomegranate, strawberries, raspberries, etc. The objective of this study was to explore whether ellagitannins from pomegranate (PETs) could ameliorate 5-FU-induced intestinal mucositis and enhance the drug's efficacy against CRC. The results showed that PETs (100 mg/kg) counteracted 5-FU-induced intestinal mucositis in rats. The number of apoptotic cells per crypt was reduced from 1.50 ± 0.21 to 0.85 ± 0.18 ( P < 0.05). Moreover, PETs induced HT-29 CRC cell death through intrinsic apoptosis, as demonstrated by dissipation of mitochondrial membrane potential, increased Bax-to-Bcl-2 ratio, and cleavage of caspase 9 and caspase 3. PETs and 5-FU combination treatments exhibited synergistic cytotoxicity against HT-29 cells with a weighted combination index of 0.3494. PETs (80 µg/mL) and 5-FU (40 µg/mL) treatments for 48 h induced 14.03 ± 0.76% and 16.42 ± 1.15% of HT-29 cells to undergo apoptosis, while the combination treatment further increased apoptosis of cells to 34.00 ± 1.54% ( P < 0.05). Combination treatment of the cells also enhanced S phase cell cycle arrest as compared with PETs or 5-FU monotherapy ( P < 0.05). These results suggest that dietary ellagitannins from pomegranate could alleviate intestinal mucositis in rats induced by 5-FU while enhancing its toxicity against HT-29 cells through potentiation of apoptosis and cell cycle arrest.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Fluoruracila/efeitos adversos , Taninos Hidrolisáveis/farmacologia , Lythraceae/química , Mucosite/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Células HT29 , Humanos , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/química , Metaloproteinases da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mucosite/induzido quimicamente , Mucosite/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
17.
J Ovarian Res ; 11(1): 15, 2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29433550

RESUMO

BACKGROUND: Whether there is a mechanistic link between FOLR1 and response to cisplatin has not been extensively examined. In this study, we determine the expression of FOLR1 in ovarian cancer and examine if FOLR1 levels influence response to cisplatin. RESULTS: (1) FOLR1 protein expression was lowest in normal ovarian tissue, higher in benign ovarian tumors, and highest in malignant tumors (P < 0.01). (2) FOLR1 expression was decreased in platinum drug-resistant ovarian tumors compared to sensitive tumors (P < 0.01). Consistent with this, FOLR1 expression in tumors progressing following cisplatin treatment was lower than levels in tumors in remission (P < 0.01). (3) FOLR1 was successfully overexpressed at both the mRNA and protein levels following transfection in SKOV3 cells. (4) SKOV3 cells with FOLR1 overexpression were the most sensitive to cisplatin treatment (IC50 = 3.60 µg/ml) and exhibited the highest inhibition rates in the presence of the drug (P < 0.05). (5) The rate of apoptosis of SKOV3 cells increased with cisplatin treatment in a dose- and time-dependent manner (P < 0.05). Cisplatin also induced S phase arrest in a concentration-dependent manner (P < 0.05). Apoptosis and S phase proportion were significantly altered by FOLR1 overexpression (P < 0.05). CONCLUSION: FOLR1 may be a useful biomarker for ovarian cancer, and it may be useful as a therapeutic application to improve sensitivity to cisplatin treatment.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptor 1 de Folato/genética , Neoplasias Ovarianas/genética , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/uso terapêutico , Monitoramento de Medicamentos , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Curva ROC , Resultado do Tratamento
18.
Molecules ; 22(7)2017 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-28672816

RESUMO

PEGylated liposomes have received much attention as pharmaceutical carriers to deliver chemotherapeutic agents for therapeutic purpose. The aim of this study was to prepare and characterize PEGylated liposome of cantharidin and investigate its therapeutic effect on human hepatocellular carcinoma treatment in vitro and in vivo. Liposomal cantharidin was evaluated for their anticancer effects in vitro using human hepatocellular carcinoma HepG2 cells and in vivo using HepG2-bearing nude mice compared to free drug. PEGylated liposome of cantharidin had a particle size of 129.9 nm and a high encapsulation efficacy of approximately 88.9%. The liposomal cantharidin had a higher anti-proliferative effect vis-à-vis free cantharidin in inducing G2/M cell cycle arrest and apoptosis. Liposomal cantharidin killed more HepG2 cancer cells at the same concentration equivalent to free cantharidin. Further study in vivo also showed that liposomal cantharidin achieved a higher tumor growth inhibition efficacy than free drug on hepatocellular carcinoma. As our study exhibited enhanced cytotoxicity against HepG2 cells and augmented tumor inhibitory effects in vivo, the results validate the potential value of cantharidin-liposome in improving the therapeutic efficacy of cantharidin for liver cancer.


Assuntos
Antineoplásicos/administração & dosagem , Cantaridina/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Cantaridina/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Lipossomos , Camundongos , Camundongos Nus , Tamanho da Partícula , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(5): 410-414, 2017 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926584

RESUMO

OBJECTIVE: To filtrate the effective fermentation products of endophytes from Glycyrrhiza uralensis by comparing expectorant effects. METHODS: Ninety Wistar rats with half males and half females were randomly divided into 9 groups(n=10):including normal control group, model group, positive control group, Glycyrrhiza decoction group, 5 groups of the fermentation products of endophytes(JTZB005,JTZB006,JTZB043,JTZB060,JTZB063). The model of phlegm blocking in lung was induced by inhaling SO2 for 30 minutes and cold wind for 10 minutes twice per day for ten days. Ten days later, 10 ml/kg normal saline was administrated in normal control group and model group, 0.08 mg/kg Fufang Beimu Lvhuaan tablets was administrated in positive control group, 0.95 g/kg Glycyrrhiza water decoction and the fermentation products of endophytes were respectively administrated in Glycyrrhiza decoction group and 5 groups of the fermentation products of endophytes. All groups were given the corresponding dose by intragastric administration once a day for seven days. The changes of rats' general activities were observed during the experimental time. Two hours after the last gavage, rats were sacrificed. The upper lobe of the right lung was removed for HE and immunohistochemical staining. Pathological of lung tissues and the expressions of aquaporin-1(AQP1)and aquaporin-5(AQP5) in lung tissue were measured. In addition, the lung tissue of middle lobe of right lung were accurately weighed, and 10% homogenate were made. The supernatant was removed by centrifugation at 3 000 r/min for ten minutes. The levels of nitric oxide (NO) was determined by nitric acid reductase method. The content of tumor necrosis factor(TNF-α) and intercellular adhesion molecule 1(ICAM-1) and the concentration of cyclooxygenase-2(COX-2) in lung tissue were measured by enzyme-linked immunosorbent(ELISA) method. RESULTS: After modeling,the levels of NO, TNF-α, ICAM-1, and the concentration of COX-2 in lung tissue were increased significantly, the expressions of AQP1 and AQP5 were decreased significantly (P<0.01). Compared with the model group, the levels of NO,TNF-α,ICAM-1 and the concentration of COX-2 in lung tissue were decreased significantly, and the expressions of AQP1 and AQP5 were increased significantly in Glycyrrhiza decoction group, JTZB005,JTZB006 and JTZB063 group(P<0.05, P<0.01). CONCLUSIONS: By filtrating, JTZB005、JTZB006、JTZB063 have expectorant effects.


Assuntos
Aquaporina 1/metabolismo , Aquaporina 5/metabolismo , Endófitos/química , Expectorantes/farmacologia , Glycyrrhiza uralensis/microbiologia , Inflamação/tratamento farmacológico , Pulmão/efeitos dos fármacos , Animais , Ciclo-Oxigenase 2/metabolismo , Feminino , Fermentação , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Óxido Nítrico/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
20.
J Ovarian Res ; 9(1): 57, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27629537

RESUMO

BACKGROUND: Ovarian cancer has the highest mortality rate of the three main malignant tumors of the female reproductive system, with a 5-year overall survival (OS) of only 20-30 %. Approximately 70 % of patients relapse without being cured. To explore the significance of serum CA125 level pre-treatment and the change pattern of CA125 post-treatment for judging prognosis and diagnosing recurrences of epithelial ovarian cancer (EOC). METHODS: A radioimmunoassay was used to continuously monitor levels of serum CA125 in 152 patients with EOC. The first test was done before surgery, then once a month after surgery for more than two consecutive years. The data were analyzed by using Kaplan-Meier curves and the log-rank test, stratified chi-square test, Pearson correlation analysis, and multivariate Cox regression analysis. RESULTS: (1) There was a relationship between patient outcomes and the serum CA125 levels before treatment and the extent and speed of serum CA125 decrease after treatment. The outcomes of patients with pre-treatment serum CA125 ≤ 35 U/ml were better than those with serum CA125 > 35 U/ml; the outcomes of patients with serum CA125 who had a logarithmic decrease or a decrease to normal within a month after treatment were also better than those with a non-logarithmic decrease or a decrease to normal that took longer than a month. (2) The results of multivariate Cox regression analysis showed that serum CA125 levels before treatment and a decreased speed of decline after treatment were independent prognostic factors; (3) The mean level of serum CA125 at relapse was 116.28 U/ml. The average time from serum CA125 increase to detection of a recurrent lesion by physical or imaging examination was 122 days. The correlation coefficient of serum CA125 level increase and tumor recurrence time was -0.674. (4) The area under the Receiver Operating Characteristic (ROC) curve of serum CA125 for diagnosing EOC recurrence was 0.879, and the sensitivity and specificity were 67.39 and 86.79 %, respectively. CONCLUSIONS: It is important to monitor serum CA125 levels pre-treatment and the change pattern of CA125 post-treatment for judging prognosis and diagnosing recurrences of EOC.


Assuntos
Biomarcadores Tumorais , Antígeno Ca-125/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Recidiva , Análise de Sobrevida , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA