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1.
J Invasive Cardiol ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787925

RESUMO

The COVID-19 pandemic led to disruptions in iodinated contrast media (ICM) production and produced a global product shortage in the spring of 2022. The ACIST CVi system is an automated contrast injector system approved by the FDA for multi-patient dosing of ICM from a single container. A transition from the traditional manifold system for contrast injection to the ACIST CVi automated injector system in our cardiac angiographic labs during the COVID-19 pandemic led to reductions in contrast waste and cost while limiting patient exposure to ICM.

2.
Georgian Med News ; (348): 117-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38807404

RESUMO

Highlighting the prospective evaluation of the surgical outcome of pedicle screw usage in the treatment of degenerative lumbar spine disease in fifty-five patients who were treated consecutively via a posterior surgical approach with pedicle screw fixation. A total of 55 consecutive patients with degenerative lumbosacral spine disease were treated at AL Mosul Teaching Hospital. Patients were included if they were between the ages of 25 and 60 years, they were admitted to the hospital with chronic back pain and or radicular pain and had a pedicle anatomy (based on a preoperative X-ray) that could accommodate surgical stabilization with PS instrumentation and fusion. Posterior surgical stabilization of the degenerative lumbar spine disease with pedicular screws was done and before discharge, each patient underwent a postoperative X-ray of the lumbosacral spine. In this series 55 patients were operated on for pedicular screw fixation with connecting bar, all patients underwent decompression except 2 cases, 47 patients with 2-level fixation and 8 patients with 3-level fixation. All patients' pain disappeared or became less, as well as paraesthesia.10 patients with lower limb neurological deficits improved. Only 5 of all patients are re-operated (three due to displacement, one due to a broken screw, and one due to a loose screw), 3 patients developed Dural tears and were treated by suturing with muscle patch, no vascular injury, no post-operative infection seen but one patient developed DVT post-operatively treated conservatively. Pedicle screw fixation facilitates the bone-fusion process, and its use is associated with a relatively low complication rate. The application of pedicle screws can be technically demanding; a thorough working knowledge of spinal anatomy and the principles of pedicle screw insertion will greatly contribute to their safe and accurate placement. These devices should be used when there is any feature of instability or due to iatrogenic instability after wide bone removal or after the destruction of facet joints.


Assuntos
Vértebras Lombares , Parafusos Pediculares , Humanos , Pessoa de Meia-Idade , Adulto , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Feminino , Masculino , Resultado do Tratamento , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Parafusos Ósseos , Estudos Prospectivos , Descompressão Cirúrgica/métodos , Região Lombossacral/cirurgia
3.
bioRxiv ; 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37214859

RESUMO

Morphogenesis requires highly coordinated, complex interactions between cellular processes: proliferation, migration, and apoptosis, along with physical tissue interactions. How these cellular and tissue dynamics drive morphogenesis remains elusive. Three dimensional (3D) microscopic imaging poses great promise, and generates elegant images. However, generating even moderate through-put quantified images is challenging for many reasons. As a result, the association between morphogenesis and cellular processes in 3D developing tissues has not been fully explored. To address this critical gap, we have developed an imaging and image analysis pipeline to enable 3D quantification of cellular dynamics along with 3D morphology for the same individual embryo. Specifically, we focus on how 3D distribution of proliferation relates to morphogenesis during mouse facial development. Our method involves imaging with light-sheet microscopy, automated segmentation of cells and tissues using machine learning-based tools, and quantification of external morphology via geometric morphometrics. Applying this framework, we show that changes in proliferation are tightly correlated to changes in morphology over the course of facial morphogenesis. These analyses illustrate the potential of this pipeline to investigate mechanistic relationships between cellular dynamics and morphogenesis during embryonic development.

4.
Poult Sci ; 101(3): 101667, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35131639

RESUMO

The present study was conducted to assess the growth performance, morphometric traits, muscle chemical composition and cholesterol content in four phenotypes of naked neck chicken (black, white-black, light brown and dark brown). A total of 320-day-old chicks, 80 from each phenotype, were randomly stratified into 20 replicates (16/replicate), according to a completely randomized design. The results showed higher final body weight, weight gain, and better FCR in both light brown and dark brown phenotypes whereas time of gains was found to be greater in dark brown phenotype. Keel length and shank circumference were greater in dark brown whereas wing spread was found to be higher in light brown phenotype. Drumstick circumference and body length did not show any significant differences (P > 0.05) across the phenotypes. Dry matter was found to be higher in white black, crude protein in black, white black and dark brown, moisture in light brown, and cholesterol content in black whereas ether extract and ash content were found to be greater in black and white black phenotypes. In conclusion, both light brown and dark brown phenotypes showed superior growth performance and morphometric traits. Similarly, from a health point of view, the dark brown and light brown phenotypes seem superior because their cholesterol content was low. Thus, it is strongly recommended that there should be a conscious effort to improve economically important traits of the light and dark brown birds to be used as dual-purpose slow growing chicken, especially in developing countries.


Assuntos
Galinhas , Carne , Animais , Galinhas/fisiologia , Colesterol , Carne/análise , Fenótipo , Aumento de Peso
5.
Polymers (Basel) ; 13(4)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562477

RESUMO

This study is based upon the functionalization of polypropylene (PP) by radical polymerization to optimize its properties by influencing its molecular weight. Grafting of PP was done at different concentrations of maleic anhydride (MAH) and benzoyl peroxide (BPO). The effect on viscosity during and after the reaction was studied by torque rheometer and melt flow index. Results showed that a higher concentration of BPO led to excessive side-chain reactions. At a high percentage of grafting, lower molecular weight product was produced, which was analyzed by viscosity change during and after the reaction. Percentage crystallinity increased by grafting due to the shorter chains, which consequently led to an improvement in the chain's packing. Prepared Maleic anhydride grafted polypropylene (MAH-g-PP) enhanced interactions in PP-PET blends caused a partially homogeneous blend with less voids.

7.
J Ethnopharmacol ; 252: 112600, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31981745

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis were prone to develop into ulcerrelated colorectal cancer with high risk of mortality. Shaoyao Decoction (SYD), a compound prescription of Chinese traditional medicine, was reported to have anti-colorectal cancer effect. Thus this study mainly investigated the protective and preventive effect of SYD against oxidative damages and inflamatory response through in vivo and in vitro experiments. AIM OF THE STUDY: Shaoyao decoction (SYD), a compound prescription of traditional Chinese medicine, is effective in treating ulcerative colitis. The increased levels of reactive oxygen species (ROS) in inflammatory cells potentially drive the development of carcinomas. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has became a novel target for the prevention of colorectal cancer (CRC). In this study, we assessed the antioxidation effect of SYD against colitis associated colorectal cancer through in vivo and in vitro experiments. MATERIALS AND METHODS: In vivo AOM/DSS-induced murine model of colon cancer and in vitro H2O2-induced oxidative stress in HT-29 cells model were conducted. To determine the antioxidant activity of SYD, protein expression of Nrf2 and its downstream genes were detected by western blot, RT-PCR and Enzyme-linked immunosorbent assay. RESULTS: Both in vivo and in vitro experiments demonstrated that SYD exerts antioxidant effect through activation of Nrf2 pathway and upregulation expression of Nrf2 downstream genes. SYD is shown to have preventive effect against colitis-associated colorectal cancer. CONCLUSIONS: These observations suggest that SYD is effective in the enhancement of antioxidant ability via activation of Nrf2 pathway and the up-regulation of Nrf2-downstream phase II enzymes expression. The anti-inflammation and antioxidant action of SYD together contributes to the prevention and treatment of ulcerrelated colorectal cancer.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Colite/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Colite/complicações , Colite/metabolismo , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Células HT29 , Humanos , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais/efeitos dos fármacos
8.
J Ethnopharmacol ; 241: 111981, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31146002

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis is one of the three high risk factors for colorectal cancer. Studies have found that about 20% of cancers are caused by repeated chronic inflammatory stimuli over a long period of time. Ulcer-related colorectal cancer is one of the main causes of death in patients with ulcerative colitis. At present, surgery is the first choice for the treatment of colorectal cancer, combined with radiotherapy and chemotherapy, which have serious side effects. However, reportedly, a compound prescription of Chinese traditional medicine Shaoyao Decoction (SYD) commonly used to treat damp-heat dysentery has anti-colorectal cancer effect. Thus this study described the effect of SYD to AOM/DSS-induced colon cancer model. AIM OF THE STUDY: In this study, modern biomedical approaches were employed for investigating the protective/preventive effects of SYD in mice with azoxymethane (AOM)/DSS-induced CRC. MATERIALS AND METHODS: The mice pretreated with AOM/DSS were randomly allocated to SYDL, SYDM, SYDH group and SASP (sulfasalazine) group. Mice without AOM/DSS treatment were randomly divided into PBS control group and SYD control group. RESULTS: It was found that SYD inhibited the production of inflammatory cytokines, TNF-α, IL-1ß, superoxide dismutase (SOD), and malonaldehyde (MDA), and increased the antioxidant indices, as measured by the mRNA expression of GR, TR, HO-1, γ-GCSc, γ-GCSm, NQO-1, UGT1A1, and UGT1A10 in AOM-treated mice. Particularly, the expressions rates of NF-κB and Ki-67 in the SYD-treated experimental groups were significantly lower than those in the model group, indicating that the proliferative ability of the CRC tissues was weaker in the SYD-treated experimental groups. Moreover, the positive levels of Nrf2 in the SYD-treated experimental groups were slightly higher than those in the model group, suggesting that SYD exhibited antioxidant activity. CONCLUSIONS: To sum up, our results suggest that SYD inhibits the development of acute/chronic colitis and prevents colitis-associated CRC by suppressing inflammation and preventing oxidative stress-induced cellular damage.


Assuntos
Anti-Inflamatórios , Anticarcinógenos , Antineoplásicos , Antioxidantes , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/prevenção & controle , Medicamentos de Ervas Chinesas , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Colite/complicações , Colite/tratamento farmacológico , Colite/metabolismo , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Neurosci Lett ; 642: 43-50, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28147225

RESUMO

Electroacupuncture (EA) has been shown to alleviate the symptoms associated with major depressive disorder; however, the underlying mechanisms remain unclear. While the mainstay treatment for depression are pharmacological agents that modulate serotonergic and/or noradrenergic activity of the brain, recent data suggest that, neurotrophins may play a larger role in the pathogenesis of depression and may offer better therapeutic potential in alleviating symptoms associated with depression. One downstream target of neurotrophins is the extracellular signal-regulated kinase (ERK)/Mitogen-activated protein kinase (MAPK) cascade, a major mediator of cellular stress often associated with clinical depression. In this study, we assessed whether the efficacy of EA is due to regulation of these novel pathways using an animal model of depression induced by chronic unpredictable mild stress (CUMS). We found that EA stimulation at specific locations, Baihui (GV20), and Yintang (GV29) ameliorated the behavioral responses of CUMS, which included reduced locomotion, decreased sucrose intake and weight loss. Furthermore, EA increased the activation of ERK and ribosomal s6 kinase (RSK) levels under stress. Both the behavioral and biochemical responses to EA were attenuated with administration of ERK inhibitor, suggesting that EA improves depression-like symptoms in stressed rats, in part, by activation of ERK signaling.


Assuntos
Comportamento Animal/fisiologia , Depressão/terapia , Eletroacupuntura , Sistema de Sinalização das MAP Quinases/fisiologia , Estresse Fisiológico/fisiologia , Estresse Psicológico/terapia , Animais , Anexina A5/metabolismo , Apoptose/fisiologia , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Resultado do Tratamento
10.
Malar J ; 15: 326, 2016 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-27315799

RESUMO

BACKGROUND: Malaria in pregnancy remains a public health problem in Nigeria. It causes maternal anaemia and adversely affects birth outcome leading to low birth weight, abortions and still births. Nigeria has made great strides in addressing the prevention and control of malaria in pregnancy. However, recent demographic survey shows wide disparities in malaria control activities across the geopolitical zones. This situation has been compounded by the political unrest and population displacement especially in the Northeastern zone leaving a significant proportion of pregnant women at risk of diseases, including malaria. The use of malaria preventive measures during pregnancy and the risk of malaria parasitaemia, anaemia and low birth weight babies were assessed among parturient women in an insurgent area. METHODS: A cross-sectional survey was conducted among 184 parturient women at Federal Medical Centre, Nguru in Yobe state, between July and November 2014. Information on demographics, antenatal care and prevention practices was collected using an interviewer-administered questionnaire. Maternal peripheral and the cord blood samples were screened for malaria parasitaemia by microscopy of Giemsa-stained blood films. The presence of anaemia was also determined by microhaemocrit method using the peripheral blood samples. Data was analysed using descriptive and analytical statistics. RESULTS: Prevalence of malaria parasitaemia, anaemia and low birth weight babies was 40.0, 41.0 and 37.0 %, respectively, and mothers aged younger than 25 years were mostly affected. Eighty (43.0 %) of the women received up to two doses of sulfadoxine-pyrimethamine for intermittent preventive treatment (IPTp-SP) during pregnancy and most, 63 (83.0 %) of those tested malaria positive received less than these. Presence of malaria infection at antenatal clinic enrollment (OR: 6.6; 95 % CI: 3.4-13.0), non-adherence to direct observation therapy for administration of IPTp-SP (OR: 4.6; 95 % CI: 2.2-9.5) and receiving

Assuntos
Controle de Doenças Transmissíveis/métodos , Transmissão de Doença Infecciosa/prevenção & controle , Pesquisa sobre Serviços de Saúde , Malária/epidemiologia , Malária/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Adolescente , Adulto , Estudos Transversais , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Microscopia , Nigéria/epidemiologia , Parasitemia/diagnóstico , Gravidez , Gestantes , Inquéritos e Questionários , Centros de Atenção Terciária , Adulto Jovem
11.
Cancer Prev Res (Phila) ; 9(7): 607-15, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27138790

RESUMO

There is a strong belief that garlic has medicinal properties and may even reduce the risk of developing certain cancers including those of the gastrointestinal tract. The chemopreventive effects of garlic may be attributed to the anti-inflammatory properties of the sulfur-containing constituents of garlic, which includes diallyl disulfide (DADS). Here, we demonstrate that DADS prevented colorectal tumorigenesis in a mouse model of colitis-induced colorectal cancer. Supplementation with 85 ppm of DADS (60 mg daily human equivalent dose) in the diet of FVB/N mice treated with chemical carcinogen azoxymethane (AOM) and colonic irritant dextran sodium sulfate (DSS) resulted in the reduction in tumor incidence, tumor number, and tumor burden by 21.54%, 47.3%, and 66.4%, respectively. Further analysis revealed that mice fed the DADS-supplemented diet resolved the initial DSS-induced inflammation faster than those on the control diet, preventing prolonged inflammation and cellular transformation. Subsequent mechanistic studies in vitro suggest that DADS chemopreventive effects are mediated through NF-κB signaling. When SW480 colorectal cancer cells were treated with DADS, NF-κB nuclear localization and activity were diminished. Interestingly, NF-κB suppression was found to be dependent on DADS inhibition of GSK-3ß, a positive regulator of NF-κB. Inhibition of GSK-3ß and loss of nuclear NF-κB activity were also observed in vivo in AOM/DSS-treated mice fed a diet supplemented with 85 ppm DADS. Our results indicate that DADS can prevent tumorigenesis by suppressing inflammation, a process largely involving GSK-3ß inhibition and consequential reduction in NF-κB nuclear localization. Cancer Prev Res; 9(7); 607-15. ©2016 AACR.


Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinogênese/efeitos dos fármacos , Neoplasias Colorretais/patologia , Dissulfetos/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colite/induzido quimicamente , Colite/complicações , Neoplasias Colorretais/etiologia , Alho/química , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Camundongos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo
12.
Clin Lung Cancer ; 17(5): 419-426, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27236386

RESUMO

BACKGROUND: Although malignant pleural mesothelioma (MPM) is generally a disease associated with more advanced age, the association of age, treatment, and outcomes has not been well-characterized. We evaluated the impact of age on outcomes in patients with MPM to provide data for use in the treatment selection process for elderly patients with potentially resectable disease. PATIENTS AND METHODS: Overall survival (OS) of patients younger than 70 and 70 years or older with Stage I to III MPM who underwent cancer-directed surgery or nonoperative management in the Surveillance, Epidemiology, and End Results database (2004-2010) was evaluated using multivariable Cox proportional hazard models and propensity score-matched analysis. RESULTS: Cancer-directed surgery was used in 284 of 879 (32%) patients who met inclusion criteria, and was associated with improved OS in multivariable analysis (hazard ratio, 0.71; P = .001). Cancer-directed surgery was used much less commonly in patients 70 years and older compared with patients younger than 70 years (22% [109/497] vs. 46% [175/382]; P < .001), but patients 70 years and older had improved 1-year (59.4% vs. 37.9%) and 3-year (15.4% vs. 8.0%) OS compared with nonoperative management. The benefit of surgery in patients 70 years and older was observed even after propensity score-matched analysis was used to control for selection bias. CONCLUSION: Surgical treatment is associated with improved survival compared with nonoperative management for both patients younger than 70 years and patients aged 70 years or older.


Assuntos
Neoplasias Pulmonares/cirurgia , Mesotelioma/cirurgia , Neoplasias Pleurais/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Mesotelioma Maligno , Estadiamento de Neoplasias , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Modelos de Riscos Proporcionais , Programa de SEER , Taxa de Sobrevida , Fatores de Tempo
13.
Artigo em Inglês | MEDLINE | ID: mdl-27019660

RESUMO

The dysregulation of TGF-ß/Smads signaling pathway has been postulated to contribute to the development of ulcerative colitis (UC) and the manifestation of clinical symptoms. Kuijie Granule is a prescription medicine used clinically in China to alleviate the symptoms associated with UC. To evaluate whether the clinical benefit of Kuijie Granule is associated with TGF-ß/Smads signaling, we measured the expression levels of TGF-ß/Smads signaling proteins (TGF-ß1, TGF-ßRII, Smad2, Smad4, Smad6, and Smad7) in the intestinal mucosa of 72 patients with UC treated with Kuijie Granule for 60 days. Colonic tissues were obtained by a virtual colonoscopy guided biopsy before and after Kuijie Granule treatment followed by pathological analysis and quantitative analysis of TGF-ß/Smads using immunohistochemistry. Kuijie Granule treatment significantly improved symptoms associated with UC, which include diarrhea, mucus production, pus and blood in stool, abdominal pain and distention, and tenesmus. The clinical benefit of Kuijie Granule treatment correlated with decreased expression of TGF-ß1 and Smad7 and increased expression of TGF-ßRII and Smad4. These clinical results indicate that Kuijie Granule can alleviate the symptoms associated with UC and modulate TGF-ß/Smads signaling.

14.
Ann Thorac Surg ; 101(3): 1037-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26822346

RESUMO

BACKGROUND: Previous studies have raised concerns that video-assisted thoracoscopic (VATS) lobectomy may compromise nodal evaluation. The advantages or limitations of robotic lobectomy have not been thoroughly evaluated. METHODS: Perioperative outcomes and survival of patients who underwent open versus minimally-invasive surgery (MIS [VATS and robotic]) lobectomy and VATS versus robotic lobectomy for clinical T1-2, N0 non-small cell lung cancer from 2010 to 2012 in the National Cancer Data Base were evaluated using propensity score matching. RESULTS: Of 30,040 lobectomies, 7,824 were VATS and 2,025 were robotic. After propensity score matching, when compared with the open approach (n = 9,390), MIS (n = 9,390) was found to have increased 30-day readmission rates (5% versus 4%, p < 0.01), shorter median hospital length of stay (5 versus 6 days, p < 0.01), and improved 2-year survival (87% versus 86%, p = 0.04). There were no significant differences in nodal upstaging and 30-day mortality between the two groups. After propensity score matching, when compared with the robotic group (n = 1,938), VATS (n = 1,938) was not significantly different from robotics with regard to nodal upstaging, 30-day mortality, and 2-year survival. CONCLUSIONS: In this population-based analysis, MIS (VATS and robotic) lobectomy was used in the minority of patients for stage I non-small cell lung cancer. MIS lobectomy was associated with shorter length of hospital stay and was not associated with increased perioperative mortality, compromised nodal evaluation, or reduced short-term survival when compared with the open approach. These results suggest the need for broader implementation of MIS techniques.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Robótica , Cirurgia Torácica Vídeoassistida/estatística & dados numéricos , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pontuação de Propensão , Porto Rico/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Mol Cell Biochem ; 406(1-2): 63-73, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25912550

RESUMO

Cryptotanshinone (CPT) is a natural compound extracted from herbal medicine that has been previously shown to possess antitumor properties in various types of human cancer cells. In the present study, we examined the potential role of CPT in the treatment of colorectal cancer. Using SW480, HCT116, and LOVO colorectal cancer cell lines, the effects of CPT on cell viability, apoptosis, and tumorigenicity were evaluated. The results showed that CPT significantly inhibited the growth and viability of SW480, HCT116, and LOVO cell lines by inducing apoptosis and prevented anchorage dependent growth on agar. In addition, CPT inhibited the activation of Signal transducer and activator of transcription 3 (Stat3) pathways in colorectal cancer cells. Stat3 is a transcription factor that mediates the expression of various genes associated with many cellular processes, such as inflammation and cell growth, and has been shown to promote several cancer types, including colorectal cancer. These findings indicate that CPT may be a potential candidate for the treatment and prevention of colorectal cancer in part by inhibiting the activation of Stat3.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Fenantrenos/farmacologia , Fator de Transcrição STAT3/metabolismo , Apoptose , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Survivina
16.
Oncotarget ; 6(10): 7365-78, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25812084

RESUMO

AMP-activated protein kinase (AMPK) is an important mediator in maintaining cellular energy homeostasis. AMPK is activated in response to a shortage of energy. Once activated, AMPK can promote ATP production and regulate metabolic energy. AMPK is a known target for treating metabolic syndrome and type-2 diabetes; however, recently AMPK is emerging as a possible metabolic tumor suppressor and target for cancer prevention and treatment. Recent epidemiological studies indicate that treatment with metformin, an AMPK activator reduces the incidence of cancer. In this article we review the role of AMPK in regulating inflammation, metabolism, and other regulatory processes with an emphasis on cancer, as well as, discuss the potential for targeting AMPK to treat various types of cancer. Activation of AMPK has been found to oppose tumor progression in several cancer types and offers a promising cancer therapy. This review evaluates the evidence linking AMPK with tumor suppressor function and analyzes the molecular mechanisms involved. AMPK activity opposes tumor development and progression in part by regulating inflammation and metabolism.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias/enzimologia , Neoplasias/terapia , Animais , Humanos , Terapia de Alvo Molecular , Neoplasias/prevenção & controle , Transdução de Sinais
17.
Mol Carcinog ; 54(10): 1096-109, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24838344

RESUMO

Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P = 0.009), a 48% reduction in tumors <2 mm, (P = 0.05); 94% reduction in tumors 2-4 mm, (P = 0.001), and 100% reduction in tumors >4 mm (P = 0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Berberina/farmacologia , Carcinogênese/efeitos dos fármacos , Colo/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Azoximetano/farmacologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/metabolismo , Ciclina D1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Feminino , Células HCT116 , Humanos , Camundongos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo , eIF-2 Quinase/metabolismo
18.
Carcinogenesis ; 35(12): 2778-86, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25280562

RESUMO

Sporadic and non-hereditary mutations account for the majority of colorectal cancers (CRC). After the loss of adenomatous polyposis coli (APC) function and activation of the ß-catenin/LEF signaling pathway, activating mutations in Kras are major drivers of sporadic CRC. Preventing the outgrowth of cells that develop sporadic mutations will decrease CRC. Resveratrol, a naturally occurring polyphenolic compound has anti-inflammatory, anti-oxidant and anti-cancer activities. We used a genetically engineered mouse model for sporadic CRC where the APC locus is knocked out and Kras is activated specifically in the distal colon to determine the effects of resveratrol on preventing and treating CRC. Feeding mice a diet supplemented with 150 or 300 ppm resveratrol (105 and 210mg daily human equivalent dose, respectively) before tumors were visible by colonoscopy resulted in a 60% inhibition of tumor production. In the 40% of mice that did develop tumors Kras expression was lost in the tumors. In a therapeutic assay where tumors were allowed to develop prior to treatment, feeding tumor bearing mice with resveratrol resulted in a complete remission in 33% of the mice and a 97% decrease in tumor size in the remaining mice. Analysis of miRNA expression in non-tumoral and tumoral colonic tissue of resveratrol treated mice showed an increased expression of miR-96, a miRNA previously shown to regulate Kras translation. These data indicate that resveratrol can prevent the formation and growth of colorectal tumors by downregulating Kras expression.


Assuntos
Proteína da Polipose Adenomatosa do Colo/fisiologia , Anticarcinógenos/uso terapêutico , Transformação Celular Neoplásica/efeitos dos fármacos , Neoplasias Colorretais/prevenção & controle , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Estilbenos/uso terapêutico , Animais , Western Blotting , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Knockout , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
19.
BMC Complement Altern Med ; 14: 153, 2014 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-24885825

RESUMO

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Conventional chemotherapy and radiotherapy are the primary therapeutic methods for lung cancer with the use of combination therapies gaining popularity. The frequency and duration of treatment, as well as, managing lung cancer by targeting multiple aspects of cancer biology is often limited by toxicity to the patient. There are many naturally occurring anticancer agents that have a high degree of efficacy and low toxicity, offering a viable and safe approach for the treatment of lung cancer. The herbs traditionally used in Chinese medicine for anticancer treatment offer great potential to enhance the efficacy of conventional therapy. In this study, we evaluated the synergistic effects of Fei-Liu-Ping (FLP) ointment in treating lung cancer; a known anticancer Chinese herbal based formula. METHODS: In this study, A549 human lung carcinoma cell line and Lewis lung carcinoma xenograft mouse model were used. In addition, we utilized an in vitro co-culture system to simulate the tumor microenvironment in order to evaluate the molecular mechanisms of FLP treatment. RESULTS: FLP treatment significantly inhibited tumor growth in the Lewis lung xenograft by 40 percent, compared to that of cyclophosphamide (CTX) of 62.02 percent. Moreover, combining FLP and CTX inhibited tumor growth by 83.23 percent. Upon evaluation, we found that FLP treatment reduced the concentration of serum pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß. In addition, we also found an improvement in E-cadherin expression and inhibition of N-cadherin and MMP9. We found similar findings in vitro when we co-cultured A549 cells with macrophages. FLP treatment inhibited A549 cell growth, invasion and metastasis, in part, through the regulation of NF-κB and altering the expression of E-cadherin, N-cadherin, MMP2 and MMP9. CONCLUSIONS: FLP exerts anti-inflammatory properties in the tumor microenvironment, which may contribute to its anticancer effects. FLP treatment may be a promising therapy for inflammation associated lung cancer treatment alone, or in combination with conventional therapies and may prevent lung cancer metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Interleucina-6/metabolismo , Macrófagos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Pomadas , Fator de Necrose Tumoral alfa/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Cancer Res ; 73(17): 5473-84, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23824743

RESUMO

Analysis of the Polyp Prevention Trial showed an association between an isorhamnetin-rich diet and a reduced risk of advanced adenoma recurrence; however, the mechanism behind the chemoprotective effects of isorhamnetin remains unclear. Here, we show that isorhamnetin prevents colorectal tumorigenesis of FVB/N mice treated with the chemical carcinogen azoxymethane and subsequently exposed to colonic irritant dextran sodium sulfate (DSS). Dietary isorhamnetin decreased mortality, tumor number, and tumor burden by 62%, 35%, and 59%, respectively. MRI, histopathology, and immunohistochemical analysis revealed that dietary isorhamnetin resolved the DSS-induced inflammatory response faster than the control diet. Isorhamnetin inhibited AOM/DSS-induced oncogenic c-Src activation and ß-catenin nuclear translocation, while promoting the expression of C-terminal Src kinase (CSK), a negative regulator of Src family of tyrosine kinases. Similarly, in HT-29 colon cancer cells, isorhamnetin inhibited oncogenic Src activity and ß-catenin nuclear translocation by inducing expression of csk, as verified by RNA interference knockdown of csk. Our observations suggest the chemoprotective effects of isorhamnetin in colon cancer are linked to its anti-inflammatory activities and its inhibition of oncogenic Src activity and consequential loss of nuclear ß-catenin, activities that are dependent on CSK expression.


Assuntos
Neoplasias Colorretais/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , beta Catenina/metabolismo , Quinases da Família src/metabolismo , Animais , Apoptose/efeitos dos fármacos , Azoximetano/toxicidade , Western Blotting , Proteína Tirosina Quinase CSK , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Sulfato de Dextrana , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Transporte Proteico , Quercetina/farmacologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , beta Catenina/genética , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/genética
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