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1.
Acad Radiol ; 31(6): 2536-2549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38614828

RESUMO

RATIONALE AND OBJECTIVES: Neurological complications associated with coronavirus disease (COVID-19) have been reported in children; however, data on neuroimaging findings remain limited. This study aimed to comprehensively examine neuroimaging patterns of COVID-19 in children and their relationship with clinical outcomes. MATERIALS AND METHODS: This retrospective cross-sectional study involved reviewing the medical records and MRI scans of 95 children who developed new neurological symptoms within 2-4 weeks of clinical and laboratory confirmation of COVID-19. Patients were categorized into four groups based on guidelines approved by the Centers for Disease Control and Prevention (CDC). Initial brain/spinal MRI was performed. Images were reviewed by three blinded radiologists, and the findings were analyzed and categorized based on the observed patterns in the brain and spinal cord. Follow-up MRI was performed and analyzed to track lesion progression. RESULTS: Encephalopathy was the most common neurological symptom (50.5%). The most common initial MRI involvement patterns were non-confluent multifocal hyperintense white matter (WM) lesions (36.8%) and ischemia (18.9%). Most patients who underwent follow-up MRI (n = 56) showed complete resolution (69.9%); however, some patients developed encephalomalacia and myelomalacia (23.2% and 7.1%, respectively). Non-confluent hyperintense WM lesions were associated with good outcomes (45.9%, P = 0.014), whereas ischemia and hemorrhage were associated with poor outcomes (44.1%, P < 0.001). CONCLUSION: This study revealed diverse neuroimaging patterns in pediatric COVID-19 patients. Non-confluent WM lesions were associated with good outcomes, whereas ischemia and hemorrhage were associated with poorer prognoses. Understanding these patterns is crucial for their early detection, accurate diagnosis, and appropriate management.


Assuntos
Encéfalo , COVID-19 , Imageamento por Ressonância Magnética , Neuroimagem , SARS-CoV-2 , Humanos , COVID-19/diagnóstico por imagem , COVID-19/complicações , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Criança , Masculino , Feminino , Pré-Escolar , Neuroimagem/métodos , Estudos Transversais , Lactente , Adolescente , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem
2.
Molecules ; 27(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35566291

RESUMO

Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine (5) or chromane (12) moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative (5c), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained.


Assuntos
Antineoplásicos , Líquidos Iônicos , Rodanina , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular
3.
Viruses ; 13(10)2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34696438

RESUMO

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Hepatite C/tratamento farmacológico , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/fisiopatologia , Egito/epidemiologia , Feminino , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/virologia , Humanos , Interleucina-13/análise , Interleucina-13/sangue , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologia , Masculino , MicroRNAs/análise , MicroRNAs/sangue , MicroRNAs/uso terapêutico , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral/métodos , Vitamina D/análise , Vitamina D/sangue
4.
Cancer Res ; 81(15): 4066-4078, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34183356

RESUMO

One-carbon (1C) metabolism has a key role in metabolic programming with both mitochondrial (m1C) and cytoplasmic (c1C) components. Here we show that activating transcription factor 4 (ATF4) exclusively activates gene expression involved in m1C, but not the c1C cycle in prostate cancer cells. This includes activation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression, the central player in the m1C cycle. Consistent with the key role of m1C cycle in prostate cancer, MTHFD2 knockdown inhibited prostate cancer cell growth, prostatosphere formation, and growth of patient-derived xenograft organoids. In addition, therapeutic silencing of MTHFD2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in preclinical prostate cancer mouse models. Consistently, MTHFD2 expression is significantly increased in human prostate cancer, and a gene expression signature based on the m1C cycle has significant prognostic value. Furthermore, MTHFD2 expression is coordinately regulated by ATF4 and the oncoprotein c-MYC, which has been implicated in prostate cancer. These data suggest that the m1C cycle is essential for prostate cancer progression and may serve as a novel biomarker and therapeutic target. SIGNIFICANCE: These findings demonstrate that the mitochondrial, but not cytoplasmic, one-carbon cycle has a key role in prostate cancer cell growth and survival and may serve as a biomarker and/or therapeutic target.


Assuntos
Ciclo do Carbono/genética , Neoplasias da Próstata/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Masculino , Camundongos , Camundongos Nus
5.
Eur Radiol ; 31(2): 674-684, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32809166

RESUMO

OBJECTIVE: The American College of Radiology (ACR) recently published the ovarian-adnexal reporting and data system (O-RADS) to provide guidelines to physicians who interpret ultrasound (US) examinations of adnexal masses (AM). This study aimed to compare the O-RADS with two other well-established US classification systems for diagnosis of AM. METHODS: This retrospective multicenter study between May 2016 and December 2019 assessed consecutive women with AM detected by the US. Five experienced consultant radiologists independently categorized each AM according to O-RADS, gynecologic imaging reporting and data system (GI-RADS), and international ovarian tumor analysis (IOTA) simple rules. Pathology and adequate follow-up were used as reference standards for calculating the validity of three US classification systems for diagnosis of AM. Kappa statistics were used to assess the inter-reviewer agreement (IRA). RESULTS: A total of 609 women (mean age, 48 ± 13.7 years; range, 18-72 years) with 647 AM were included. Of the 647 AM, 178 were malignant and 469 were benign. Malignancy rates were comparable to recommended rates by previous literature in O-RADS and IOTA, but higher in GI-RADS. O-RADS had significantly higher sensitivity for malignancy than GI-RAD and IOTA (p = 0.003 and 0.0007, respectively), but non-significant slightly lower specificity (p > 0.05). O-RADS, GI-RADS, and IOTA showed similar overall IRA (κ = 0.77, 0.69, and 0.63, respectively) with a tendency toward higher IRA with O-RADS than with GI-RADS and IOTA. CONCLUSIONS: O-RADS compares favorably with GI-RADS and IOTA. O-RADS had higher sensitivity than GI-RADS and IOTA simple rules with relatively similar specificity and reliability. KEY POINTS: • The malignancy rates were comparable to recommended rates by previous literature in O-RADS and IOTA, but higher in GI-RADS. • The O-RADS had significantly higher sensitivity for malignancy than GI-RADS and IOTA (96.8% vs 92.7% and 92.1%; p = 0.003 and 0.0007, respectively), but non-significant slightly lower specificity (92.8% vs 93.6% and 93.2%, respectively; p > 0.05). • The O-RADS, GI-RADS, and IOTA showed similar overall inter-reviewer agreement (IRA) (κ = 0.77, 0.69, and 0.63, respectively), with a tendency toward higher IRA with O-RADS than with GI-RADS and IOTA.


Assuntos
Doenças dos Anexos , Neoplasias Ovarianas , Doenças dos Anexos/diagnóstico por imagem , Adulto , Sistemas de Dados , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia
6.
Molecules ; 25(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365503

RESUMO

Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. Brassica nigra (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of B. nigra seeds against A549 and H1299 human non-small cell lung cancer cell lines. B. nigra extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. B. nigra extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with B. nigra extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, B. nigra extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, B. nigra extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that B. nigra seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Mostardeira/química , Extratos Vegetais/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Replicação do DNA , Relação Dose-Resposta a Droga , Transição Epitelial-Mesenquimal/genética , Humanos
7.
Food Chem ; 306: 125640, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606625

RESUMO

Combination of pesticides; acetamiprid, flutolanil and etofenprox are usually used for tomato fruits for protecting them against pest infection. Generally, pesticides, residues could be one of the health hazard sources. Two specific simple sensitive chromatographic methods are developed for simultaneous estimation of the concerning pesticides' residues using simple economic steps of field sample preparation. The first method is HP- TLC method. Hexane: methanol: acetone: glacial acetic acid (8:2:0.5:0.1, by volume) is proposed as a developing system. The second one is RP- HPLC. Acetonitrile: water (75:25, v/v) is proposed as a mobile phase. The recommended methods are completely validated regarding ICH guidelines. Their means percentages and standard deviations of accuracy range 100.32 ±â€¯0.89 to 99.27 ±â€¯0.9. The methods' repeatability and intermediate precision relative standard deviation percentages range 0.395-0.894. They are successfully applied for estimating the pesticides in pure and commercial forms and field samples.


Assuntos
Manipulação de Alimentos , Resíduos de Praguicidas/análise , Piretrinas/análise , Solanum lycopersicum/química , Cromatografia Líquida de Alta Pressão/métodos , Frutas/química , Segurança
8.
Clin Oncol (R Coll Radiol) ; 32(4): 259-265, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31708350

RESUMO

AIMS: To evaluate focal high dose rate (HDR) brachytherapy in locally recurrent prostate cancer. MATERIALS AND METHODS: Patients with biochemical relapse after non-surgical primary treatment for localised prostate cancer were selected after a negative screen for metastatic disease. Template mapping biopsies combined with multiparametric magnetic resonance imaging were used to identify the location of the tumour and the focal clinical target volume. The planning aim dose prescription was 19 Gy. Outcome measures were biochemical relapse-free survival and toxicity using International Prostate Symptom Score and Common Terminology Criteria for Adverse Events (version 4.0) scores. RESULTS: Between March 2013 and December 2018, 50 patients underwent salvage HDR brachytherapy. The median follow-up was 21 months (range 1-53). Biochemical progression-free survival at 2 and 3 years was 63% and 46%, respectively. On multivariate analysis, only prostate-specific antigen nadir ≤0.5 ng/ml post-salvage (P = 0.03, hazard ratio 0.04) was associated with biochemical progression-free survival. Relapse was associated with distant metastases in 11/13 patients in whom this was investigated. Late grade 3 genitourinary toxicities were gross haematuria (three patients), severe lower urinary tract symptoms (two patients), erectile dysfunction (one patient) and urethral stricture requiring surgery (four patients). No acute and late grade 4 or 5 genitourinary and no grade 3 or higher gastrointestinal toxicities were recorded. CONCLUSIONS: Focal salvage HDR monotherapy achieves biochemical control in 46% of patients at 3 years with acceptable toxicity rates in selected patients. Biochemical relapse was related to a post-salvage prostate-specific antigen nadir of ≥0.5 ng/ml. Long-term outcomes are needed to assess the impact on the natural history of prostate cancer in these patients.


Assuntos
Braquiterapia/métodos , Neoplasias da Próstata/cirurgia , Terapia de Salvação/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Neoplasias da Próstata/patologia
9.
Oncogene ; 38(35): 6301-6318, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31312022

RESUMO

Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One such critical pathway in eukaryotic cells is the unfolded protein response (UPR) that is important in normal physiology as well as disease states, including cancer. Since UPR can serve as a lever between survival and death, regulated control of its activity is critical for tumor formation and growth although the underlying mechanisms are poorly understood. Here we show that one of the main transcriptional effectors of UPR, activating transcription factor 4 (ATF4), is essential for prostate cancer (PCa) growth and survival. Using systemic unbiased gene expression and proteomic analyses, we identified a novel direct ATF4 target gene, family with sequence similarity 129 member A (FAM129A), which is critical in mediating ATF4 effects on prostate tumorigenesis. Interestingly, FAM129A regulated both PERK and eIF2α in a feedback loop that differentially channeled the UPR output. ATF4 and FAM129A protein expression is increased in patient PCa samples compared with benign prostate. Importantly, in vivo therapeutic silencing of ATF4-FAM129A axis profoundly inhibited tumor growth in a preclinical PCa model. These data support that one of the canonical UPR branches, through ATF4 and its target gene FAM129A, is required for PCa growth and thus may serve as a novel therapeutic target.


Assuntos
Fator 4 Ativador da Transcrição/fisiologia , Biomarcadores Tumorais/fisiologia , Proteínas de Neoplasias/fisiologia , Neoplasias da Próstata/metabolismo , Resposta a Proteínas não Dobradas/genética , Animais , Proliferação de Células/genética , Estresse do Retículo Endoplasmático/genética , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais/genética , Células Tumorais Cultivadas
10.
Viruses ; 10(7)2018 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-29937515

RESUMO

Hepatitis C virus is a hepatotropic virus that is transmitted parenterally. Viral infections are usually associated with modulations of the immune cells, leading to enhanced viral survival and spreading, and accordingly, life-threatening complications. Recently, it has been proposed that a new subset of T-helper, named T-helper 9, is involved in the pathogenesis of different immunopathological conditions, such as allergies, tumors, and viral infections. Some studies reported a protective role, and others described a pathogenic potential for the T-helper 9 cells. Here, we present evidence that T-helper 9 cells are dynamically increased with increasing the pathogenic strategy for hepatitis C virus (HCV). Furthermore, viral clearance is associated with a decrease in T-helper 9. The increase in T-helper 9 was paralleled with an increase in its receptor expression. Taken together, our data suggest that T-helper 9 cells play an important role in the pathogenesis of HCV, and is directly associated with HCV-related complications.


Assuntos
Hepacivirus/patogenicidade , Hepatite C Crônica/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepacivirus/imunologia , Humanos , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-9/genética
12.
Br J Anaesth ; 119(6): 1127-1134, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29136086

RESUMO

Background: The threshold of intraoperative urine output below which the risk of acute kidney injury (AKI) increases is unclear. The aim of this retrospective cohort study was to investigate the relationship between intraoperative urine output during major abdominal surgery and the development of postoperative AKI and to identify an optimal threshold for predicting the differential risk of AKI. Methods: Perioperative data were collected retrospectively on 3560 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or oesophageal resection) at Kyoto University Hospital. We evaluated the relationship between intraoperative urine output and the development of postoperative AKI as defined by recent guidelines. Logistic regression analysis was performed to adjust for patient and operative variables, and the minimum P -value approach was used to determine the threshold of intraoperative urine output that independently altered the risk of AKI. Results: The overall incidence of AKI in the study population was 6.3%. Using the minimum P -value approach, a threshold of 0.3 ml kg -1 h -1 was identified, below which there was an increased risk of AKI (adjusted odds ratio, 2.65; 95% confidence interval, 1.77-3.97; P <0.001). The addition of oliguria <0.3 ml kg -1 h -1 to a model with conventional risk factors significantly improved risk stratification for AKI (net reclassification improvement, 0.159; 95% confidence interval, 0.049-0.270; P =0.005). Conclusions: Among patients undergoing major abdominal surgery, intraoperative oliguria <0.3 ml kg -1 h -1 was significantly associated with increased risk of postoperative AKI.


Assuntos
Abdome/cirurgia , Injúria Renal Aguda/diagnóstico , Complicações Intraoperatórias/urina , Oligúria/urina , Complicações Pós-Operatórias/diagnóstico , Injúria Renal Aguda/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/urina , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
Environ Geochem Health ; 39(1): 125-137, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26979054

RESUMO

Cairo city is the largest populated area along the whole course of River Nile with a wide range of anthropogenic activities. Efforts to restore fish habitat and recreational use of the river have raised concerns about its water, sediment and biota quality. This study provides a baseline data on the levels of PCBs and trace metals in River Nile along Cairo sector and implements the formulation of monitoring activities of the river's pollution status. Water, sediment and Nile tilapia (Oreochromis niloticus) samples were collected during summer season, 2013 from two sites, up- and downstream, for detection and determination of 11 PCB congeners (PCBs 28, 44, 52, 70, 101, 105, 118, 138, 152, 180 and 192) as well as six trace metals (Cu, Zn, Mn, Cd, Pb and Fe). Evidences of long- or short-term exposures to these contaminants as well as its accumulation tendency were assessed by integrating the obtained analytical results of biotic and abiotic components of this aquatic ecosystem. All calculated lifetime cancer risk values for PCBs showed unacceptable risk of cancer for human consumers at both normal and subsistence fish consumption rates. The calculated hazard index for total PCBs indicates that fish are not safe for human consumption except in site 1 at normal consumption rate. Meanwhile, trace metals do not pose unacceptable risks at both consumption rates except for Pb in site 1 at subsistence consumption rate.


Assuntos
Metais/análise , Bifenilos Policlorados/análise , Medição de Risco , Oligoelementos/análise , Humanos , Rios
15.
Artigo em Inglês | MEDLINE | ID: mdl-27791821

RESUMO

A biomonitoring study was conducted to evaluate levels of eleven polycyclic aromatic hydrocarbons (PAHs) in water, sediment and wild Nile tilapia (Oreochromis niloticus) samples collected up- and downstream of Cairo sector of the River Nile, Egypt. The scaled mass index (SMI), as a fish body mass-length relationship, performed better in indicating the ecosystem and fish conditions. The total PAHs in water samples had a range of 0.0156-0.0269 mg/L, while that in sediment samples ranged from 0.723 to 1.078 mg/kg dry weight and that in fish muscles ranged from 4.065 to 10.033 mg/kg wet weight. Pollutant source appraisal was determined by diagnostic ratios and proved the predominance of pyrogenic sources in water, petrogenic sources in fish, and mixed source origin in sediment. Human health risks associated with fish consumption showed that non-cancer adverse health effects are not expected to occur but the calculated lifetime cancer risk (LCR) for the total PAHs proved that the fish muscles are not safe for human consumption at both sites. Regular monitoring programs and mitigation efforts should be considered in the near future along such areas heavily influenced by human activities.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos/química , Rios , Poluentes Químicos da Água/química , Animais , Ecossistema , Egito , Monitoramento Ambiental , Peixes , Humanos , Densidade Demográfica , Medição de Risco
17.
Cancer Gene Ther ; 23(4): 107-13, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26987291

RESUMO

Molecules essential for the induction of immunogenic cell death (ICD) are called damage-associated molecular patterns (DAMPs). The effects of oncolytic herpes simplex virus type 1 (HSV-1) on the production of DAMPs were examined in squamous cell carcinoma (SCC) cells. The cytopathic effects of HSV-1 RH2 were observed in mouse SCCVII cells infected at a high multiplicity of infection (MOI), and the amounts of viable cells were decreased. After being infected with RH2, ATP and high mobility group box 1 (HMGB1) were released extracellulary, while calreticulin (CRT) translocated to the cell membrane. A flow-cytometric analysis revealed an increase in the number of annexin-V and propidium iodide (PI)-stained cells; and the amount of cleaved poly (ADP-ribose) polymerase (PARP) was increased. The killing effect of RH2 was reduced by pan-caspase inhibitor z-VAD-fmk and the caspase-1 inhibitor z-YVAD-fmk, suggesting the involvement of apoptosis and pyroptosis. In C3H mice bearing synergic SCCVII tumors, the growth of tumors injected with the supernatant of RH2-infected cells was less than that of tumors injected with phosphate-buffered saline (PBS). These results indicate that oncolytic HSV-1 RH2 produces DAMPs from SCC cells to induce cell death. This may contribute to the enhancement of tumor immunity by oncolytic HSV-1.


Assuntos
Morte Celular/imunologia , Herpesvirus Humano 1/imunologia , Vírus Oncolíticos/imunologia , Trifosfato de Adenosina/metabolismo , Animais , Calreticulina/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Células Cultivadas , Efeito Citopatogênico Viral , Modelos Animais de Doenças , Citometria de Fluxo , Proteína HMGB1/metabolismo , Camundongos , Terapia Viral Oncolítica , Poli(ADP-Ribose) Polimerases/metabolismo , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Integr Cancer Ther ; 14(6): 525-45, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26130745

RESUMO

Hepatocellular carcinoma (HCC) is one of the common cancers and lethal diseases worldwide. Both oxidative stress and chronic inflammation contribute to the pathogenesis of HCC. Because of limited treatment options and a grave prognosis of HCC, preventive management has been emphasized. The marine macroalgae Ulva lactuca (Ulvaceae) is consumed by humans and livestock because of its nutritional value. Recent studies showed that various extracts of U. lactuca possess antiviral, antiplasmodial, antinephrotoxic, antioxidant, and anti-inflammatory properties. However, very limited information is available on anticancer potential of U. lactuca with no reports on liver cancer chemopreventive efficacy of this marine algae. Accordingly, the present study was initiated to evaluate the possible antihepatocarcinogenic effects and antioxidant mechanisms of action of various U. lactuca extracts against a clinically relevant rodent model of HCC. Initiation of hepatocarcinogenesis was performed in Sprague-Dawley rats by a single injection of dietary carcinogen diethylnitrosamine (DENA, 200 mg/kg, intraperitoneally), followed by promotion with phenobarbital (0.05%) in drinking water. The rats were fed with daily oral dose (50 mg/kg) of polysaccharide sulfate or aqueous extract of U. lactuca for 2, 12, and 24 weeks. At these timepoints, blood samples were taken to measure hepatic injury markers, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, and bilirubin. The liver tissue was harvested for measurement of hepatic oxidative indices, including lipid peroxidation, reduced glutathione, nitric oxide, catalase, superoxide dismutase, glutathione reductase, and glutathione S-transferase. Hepatic histopathology, immunohistochemical analysis of cell proliferation and apoptosis by DNA fragmentation assay were performed. Our results clearly indicate that sulfated polysaccharides of U. lactuca exert a marked chemoprevention of DENA-initiated hepatocarcinogenesis through inhibition of abnormal cell proliferation and induction of apoptosis. A modest inhibition rat liver carcinogenesis was observed with the aqueous extract. The sulfated polysaccharides altered serum parameters of hepatic damage and modulated various components of the hepatic enzymatic and nonenzymatic antioxidant defense systems. The sulfated polysaccharides from U. lactuca may have unique properties of providing protection against DENA-induced oxidative stress which could contribute to chemoprevention of experimental hepatocarcinogenesis. U. lactuca sulfated polysaccharides could be developed as chemopreventive and therapeutic drug against human HCC.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas Experimentais/prevenção & controle , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Ulva/química , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dietilnitrosamina/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fenobarbital/toxicidade , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
19.
Cancer Gene Ther ; 22(3): 163-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25656776

RESUMO

Low-intensity ultrasound is a useful method to enhance the delivery of drugs to target cells via a range of mechanisms including the transient formation of micropores in the cell membrane, a process known as sonoporation. The effect of ultrasound on oncolytic herpes simplex virus type-1 (HSV-1) infection in oral squamous cell carcinoma (SCC) was examined. Human SCC cell line SAS and oncolytic HSV-1 RH2, which was deficient in the neurovirulent γ134.5 gene and exhibited cell fusion actions, were used. Cells grown in multi-well plates were infected with HSV-1 and exposed to ultrasound in the presence or absence of microbubbles after an adsorption period. The number of plaques was significantly greater than that of the untreated control. SAS cells were inoculated subcutaneously into nude mice and tumors were produced. Tumors were injected with HSV-1 RH2 with or without microbubbles and then exposed to ultrasound through the covering skin. The amount of the virus in tumor tissues 3 days after the injection was higher in tumors treated with HSV-1 RH2 and ultrasound than in tumors treated with RH2 only. The expression of the HSV-1 antigen was also increased by ultrasound and microbubbles. Tumor growth was suppressed with HSV-1 RH2 in combination with ultrasound, especially with microbubbles. These results indicated that ultrasound increased the efficiency of the HSV-1 infection in SAS cells and nude mouse tumors. This method can potentially be useful to enhance the antitumor effects of oncolytic HSV-1 on head and neck cancer treatment.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Herpesvirus Humano 1/genética , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Animais , Antígenos Virais/biossíntese , Antígenos Virais/genética , Linhagem Celular Tumoral , Chlorocebus aethiops , Feminino , Herpesvirus Humano 1/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Vírus Oncolíticos/metabolismo , Terapia por Ultrassom , Células Vero
20.
Bone Joint J ; 96-B(6): 795-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24891581

RESUMO

We examined the outcomes and levels of patient satisfaction in 202 consecutive cases of ultrasound-guided supraclavicular brachial plexus block (SBPB) in upper limb surgery performed between September 2007 and March 2010. All blocks were performed by orthopaedic surgeons using ultrasound visualisation with a high-frequency linear probe. The probe was placed in the coronal-oblique plane in the supraclavicular fossa, and the puncture was 'in-plane' from lateral to medial. Most of the blocks were performed with 0.75% ropivacaine/1% lidocaine (1:1), with or without adrenaline in 1:200 000 dilution. In 201 patients (99.5%) the brachial plexus block permitted surgery without conversion to general anaesthesia. The mean procedure time for block was 3.9 min (2 to 12), the mean waiting time for surgery was 34.1 min (10 to 64), the mean surgical time was 75.2 min (6 to 232), and the mean duration of post-anaesthetic analgesia was 437 min (171 to 992). A total of 20 patients (10%) developed a transient Horner's syndrome. No nerve injury, pneumothorax, arterial puncture or systemic anaesthetic toxicity were recorded. Most patients (96.7%) were satisfied with ultrasound-guided SBPB. This study demonstrates the efficacy and safety of ultrasound-guided SBPB for orthopaedic surgery on the upper limb.


Assuntos
Anestésicos Locais/administração & dosagem , Plexo Braquial/efeitos dos fármacos , Plexo Braquial/diagnóstico por imagem , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Adulto , Clavícula , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Inquéritos e Questionários , Resultado do Tratamento , Extremidade Superior/cirurgia
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