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1.
PLoS Pathog ; 17(12): e1010098, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860863

RESUMO

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.


Assuntos
Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/virologia , Influenza Humana/virologia , Vírus Reordenados/genética , Proteínas da Matriz Viral/metabolismo , Zoonoses Virais/virologia , Animais , Galinhas/virologia , Humanos , Vírus da Influenza A/genética , Liberação de Vírus
2.
Virol J ; 20(1): 288, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049836

RESUMO

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.


Assuntos
Infecções por Vírus Epstein-Barr , Herpes Simples , Infecções por Herpesviridae , Herpesviridae , Herpesvirus Humano 1 , Neoplasias do Colo do Útero , Humanos , Feminino , Herpesvirus Humano 4 , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 2
3.
Eur J Neurol ; 28(9): 3012-3021, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34192398

RESUMO

BACKGROUND AND PURPOSE: To determine the long-term survival outcomes of and prognostic factors for survival in patients with a ruptured intracranial aneurysm (RIA) who underwent endovascular coil embolization or surgical clipping. METHODS: We selected patients who had received a diagnosis of RIA between January 1, 2011 and December 31, 2017. Propensity score matching was performed, and Cox proportional hazards model curves were plotted to analyze all-cause mortality in patients undergoing different treatments. RESULTS: The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping groups, respectively) who were eligible for inclusion. In multivariate Cox regression analyses, the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for endovascular coil embolization compared with surgical clipping were 0.87 (95% CI, 0.79-0.97). The aHRs for the ages of 65 to 74, 75 to 84, and ≥85 years compared with the ages of 20 to 64 years were 1.82 (95% CI, 1.60-2.07), 3.35 (95% CI, 2.93-3.84), and 6.99 (95% CI, 5.51-8.86), respectively. Surgical clipping; old age; male sex; treatment during 2011 to 2013; presence of diabetes, congestive heart failure, hypertension, chronic kidney disease, or end-stage renal disease; history of stroke or transient ischemic attack; Charlson Comorbidity Index ≥2; attendance of nonacademic hospitals; and low income were significant independent prognostic factors for poor survival. CONCLUSIONS: Compared with surgical clipping, endovascular coil embolization led to more favorable survival outcomes in patients with RIAs.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Adulto , Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Estudos de Coortes , Humanos , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Resultado do Tratamento , Adulto Jovem
4.
J Sci Food Agric ; 100(12): 4612-4617, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32418235

RESUMO

BACKGROUND: Irradiation can cause lipid oxidation of fish. This study aimed to examine the effect of radiation (method, dose and dose rate) on the acid value (AV), peroxide value (PV), thiobarbituric acid reactive substances (TBARS) content and fatty acid profile of fresh and freeze-dried largemouth bass flesh. RESULTS: AV, PV and TBARS presented a dose-dependent increase in fish meat for both cobalt-60 (60 Co) and electron beam (EB) irradiation. With a 6 kGy dose of radiation, all measured indices in the 60 Co group were significantly higher than those in the EB group (P < 0.05 or P < 0.01). With a 3 kGy dose of radiation, AV, PV and TBARS in the 200 Gy min-1 dose rate group were significantly lower than those in the 2 and 80 Gy min-1 groups (P < 0.05). After 60 Co irradiation, AV, PV and TBARS in most fresh samples were significantly higher than those in freeze-dried samples (P < 0.01). And 60 Co irradiation decreased the unsaturated fatty acid (UFA) content in fresh samples and increased the UFA content in freeze-dried samples. Our study indicated that 60 Co irradiation, particularly at a low dose rate, accelerated lipid oxidation in fish meat. A large amount of muscle moisture enhances the amount of UFA loss in fish meat during 60 Co irradiation. CONCLUSIONS: A low dose (3 kGy) of EB irradiation, a high dose rate (200 Gy min-1 ) of 60 Co irradiation or freeze-drying treatment can alleviate the lipid oxidation of largemouth bass meat. © 2020 Society of Chemical Industry.


Assuntos
Radioisótopos de Cobalto/química , Irradiação de Alimentos/métodos , Lipídeos/química , Carne/efeitos da radiação , Animais , Bass , Ácidos Graxos Insaturados/química , Carne/análise , Oxirredução
5.
Rev Esp Enferm Dig ; 112(10): 797-804, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32338027

RESUMO

BACKGROUND: long noncoding RNAs (lncRNAs) have attracted attention recently. However, many inconsistencies frequently appeared for the early diagnosis of digestive tract cancers (DTCs). We performed this meta-analysis to describe the diagnostic performance of lncRNAs in the discrimination of DTCs. METHODS: data were extracted from PubMed, Web of Science, Embase, and Cochrane Library. Their quality was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Such parameters as sensitivity and specificity were included for pooled analyses. The STATA 12.0 and Meta-Disc 1.4 software packages were used to perform the statistical analysis. RESULTS: sixty-nine papers were included in this meta-analysis. The pooled analysis of DTCs showed that lncRNAs had a sensitivity of 0.78 and a specificity of 0.80. The area under the summary ROC curve (AUC) was 0.86. For gastric cancer (GC), the pooled sensitivity and specificity were 0.77 (95 % CI: 0.72-0.81) and 0.75 (95 % CI: 0.71-0.79), respectively, and the AUC was 0.83. For colorectal cancer (CRC), these three parameters were 0.82 (95 % CI: 0.76-0.86), 0.84 (95 % CI: 0.79-0.88), and 0.90, respectively. For esophageal cancer (EC) sensitivity was 0.74 (95 % CI: 0.67-0.80) and specificity reached 0.86 (95 % CI: 0.72-0.93), with an AUC of 0.82. CONCLUSIONS: LncRNAs show potential diagnostic value for discrimination between DTCs.


Assuntos
Neoplasias Gastrointestinais , RNA Longo não Codificante , Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Humanos , RNA Longo não Codificante/genética
6.
Wei Sheng Yan Jiu ; 48(1): 82-88, 2019 Jan.
Artigo em Zh | MEDLINE | ID: mdl-31032773

RESUMO

OBJECTIVE: To understand the effects of ambient air pollution on the prevalence of acute respiratory diseases and symptoms among adults in three cities in the Yangtze River Delta. METHODS: During September to November 2015, 4144 permanent residents aged 18 years and above from four investigation sites in three cities in the Yangtze River Delta were randomly surveyed by questionnaire. Daily concentrations of air pollutants, including PM_(2. 5), NO_2、O_3、CO and SO_2 nearest to the investigation sites were collected from the department of environmental protection. Logistic regression was used to analyze the association between air pollution and acute respiratory diseases and symptoms after other risk factors were adjusted. RESULTS: The prevalence of acute respiratory diseases and symptoms in two weeks among adults were 0. 99% and 3. 88%, respectively. Chemicals related to air pollution(OR=2. 339, 95%CI 1. 156-4. 734) and allergy(OR=4. 857, 95%CI 2. 279-10. 350) were the risk factors of acute respiratory diseases in two weeks among adults while occupational hazards such as toxic chemicals and high temperature(OR=1. 796, 95%CI 1. 220-2. 644), family history of respiratory diseases(OR=2. 670, 95%CI 1. 865-3. 823) and allergy(OR=3. 703, 95%CI 2. 395-5. 725) were the risk factor of respiratory symptoms in two weeks among adults. In addition, the average exposure level of PM_(2. 5)in two weeks was associated with acute respiratory diseases(OR=1. 014, 95%CI 1. 000-1. 028) and symptoms(OR=1. 025, 95%CI 1. 018-1. 033) in two weeks among adults. CONCLUSION: The increases of the prevalence of acute respiratory diseases and symptoms among adults are associated with ambient air pollution in three cities in the Yangtze River Delta.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pneumopatias , Adulto , Poluentes Atmosféricos/efeitos adversos , China/epidemiologia , Cidades , Humanos , Pneumopatias/epidemiologia , Material Particulado , Rios , Fatores de Tempo
7.
Immunology ; 153(2): 246-252, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28892130

RESUMO

Programmed death-1 (PD-1) plays an important role in protecting against inflammation and myocyte damage in T-cell-mediated myocarditis. To understand whether fibrinogen-like protein-2 (FGL2) can affect the role of the PD-1/PD-L1 pathway in experimental autoimmune myocarditis (EAM), we investigated cardiac function in EAM rats over-expressing FGL2. Over-expression of FGL2 significantly decreased PD-1 and deteriorated cardiac function in rats with autoimmune myocarditis. Histopathology revealed increased inflammatory cell infiltrate in EAM-FGL2 rats compared with the control groups (EAM, EAM-GFP and NC). Notably, transcription factor forkhead box P3 (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) protein and mRNA levels were statistically (P < 0·05) increased in EAM rats. We also found that interferon-γ, interleukin-6, interleukin-17 and brain natriuretic peptide levels were profoundly increased in serum of FGL2 over-expressing EAM rats. Hence, FGL2 plays an important role in the pathogenesis of autoimmune myocarditis that also involves the PD-1/PD-L1 pathway. Our findings may provide novel therapeutic targets for the treatment of immune-induced heart injury.


Assuntos
Doenças Autoimunes/imunologia , Citocinas/imunologia , Fibrinogênio/imunologia , Miocardite/imunologia , Receptor de Morte Celular Programada 1/imunologia , Animais , Doenças Autoimunes/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/imunologia , Miocardite/patologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Ratos , Ratos Endogâmicos Lew
8.
World J Urol ; 36(9): 1373-1381, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29610963

RESUMO

OBJECTIVE: This study is a meta-analysis and aims to determine the value of urinary survivin for detecting bladder cancer (BC) on the basis of preceding statistical performance and to compare their diagnostic value. MATERIALS AND METHODS: Considering that the urinary survivin data were from both RNA and protein levels, the key words "bladder cancer" AND "survivin" and "bladder cancer" AND "survivin RNA" were used; and PubMed, Web of Science, and Cochrane Library were systematically searched to identify relevant articles. The methodological quality of each study was assessed by QUADAS-2. Data were analyzed by STATA 12.0 and Meta-disc v.1.4 software package. A random-effects model was used and subgroup analysis was carried out to identify possible sources of heterogeneity. RESULTS: Nine articles for survivin protein test with 789 patients and 684 controls, and 12 articles for survivin RNA test with 880 patients and 922 controls were identified. The results showed that the pooled sensitivity was 0.79 (95% CI 0.73, 0.84), specificity was 0.87 (95% CI 0.79, 0.92) of the survivin protein test for bladder cancer, and the sensitivity and specificity was 0.84 (95% CI 0.79, 0.88) and 0.94 (95% CI 0.89, 0.97) of the survivin RNA test. The AUC of the two approaches was 0.89 (95% CI 0.86, 0.91) and 0.94 (95% CI 0.92, 0.96), respectively. CONCLUSIONS: The survivin protein and survivin RNA both had great potential as biomarkers for BC detection, and survivin RNA showed higher accuracy than survivin protein on BC diagnosis.


Assuntos
Survivina/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Humanos , RNA/urina , Sensibilidade e Especificidade , Software , Survivina/genética
9.
Nanotechnology ; 29(31): 315301, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-29770773

RESUMO

Molecular rotors, motors and gears play important roles in artificial molecular machines, in which rotor and motor matrices are highly desirable for large-scale bottom-up fabrication of molecular machines. Here we demonstrate the fabrication of a highly ordered molecular rotor matrix by depositing nonplanar dipolar titanyl phthalocyanine (TiOPc, C32H16N8OTi) molecules on a Moiré patterned dipolar FeO/Pt(111) substrate. TiOPc molecules with O atoms pointing outwards from the substrate (upward) or towards the substrate (downward) are alternatively adsorbed on the fcc sites by strong lateral confinement. The adsorbed molecules, i.e. two kinds of molecular rotors, show different scanning tunneling microscopy images, thermal stabilities and rotational characteristics. Density functional theory calculations clarify that TiOPc molecules anchoring upwards with high adsorption energies correspond to low-rotational-rate rotors, while those anchoring downwards with low adsorption energies correspond to high-rotational-rate rotors. A robust rotor matrix fully occupied by low-rate rotors is fabricated by depositing molecules on the substrate at elevated temperature. Such a paradigm opens up a promising route to fabricate functional molecular rotor matrices, driven motor matrices and even gear groups on solid substrates.

10.
JTO Clin Res Rep ; 5(2): 100630, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361739

RESUMO

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody-drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.

11.
J Cancer Res Clin Oncol ; 150(8): 395, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180576

RESUMO

Traditionally, the D1228 E/G/H/N mutation has been thought to cause Type I MET-TKI resistance. We reported a 75-year-old female with non-small cell lung cancer harboring MET exon 14 skipping mutation, who developed acquired MET D1228H mutation induced by capmatinib treatment. Interestingly, the patient demonstrated marked response to second-line savolitinib treatment with the duration of response of 19 months and several additional metastatic lesions appeared. Pathological assessment of rebiopsy sample showed adenocarcinoma and targeted next-generation sequencing revealed the loss of MET D1228H mutation and presence of MET p.Y1230N mutation. In response, the treatment regimen was amended to include a daily administration of 60 mg of cabozantinib, which resulted in moderate size reduction of the tumours. The switch of resistance mutations indicated that different type Ib MET inhibitors may exhibit distinct mechanisms of resistance. We call for futher studies on resistance based on patient-derived pre-clinical models including patient-derived tumor-like cell clusters, patient-derived organoids, and patient-derived xenografts.


Assuntos
Adenocarcinoma de Pulmão , Resistencia a Medicamentos Antineoplásicos , Éxons , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas c-met , Humanos , Proteínas Proto-Oncogênicas c-met/genética , Feminino , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Benzamidas , Acrilamidas/uso terapêutico , Triazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Piridinas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Imidazóis , Pirazinas
12.
BMJ Open ; 14(9): e082314, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327050

RESUMO

OBJECTIVES: To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2. DESIGN: A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan. SETTING: All primary health institutions in Anning, Yunnan Province, China, from April to May 2023. PARTICIPANTS: A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Long COVID was measured by participants' self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants' ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term. RESULTS: We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction <0.001) in long COVID. CONCLUSION: The interaction between ES and healthy lifestyle in long COVID was prominent. Comprehensive strengthened economic support for patients recovering from COVID-19, especially for those with low healthy lifestyle, should be implemented to prevent and manage long COVID symptoms.


Assuntos
Status Econômico , Estilo de Vida Saudável , Síndrome de COVID-19 Pós-Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Estudos Transversais , População do Leste Asiático , Exercício Físico , Comportamentos Relacionados com a Saúde , Pandemias , Fumar/epidemiologia , Síndrome de COVID-19 Pós-Aguda/epidemiologia
13.
J Thorac Oncol ; 18(8): 1082-1093, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37085031

RESUMO

INTRODUCTION: To determine the effect of statin use during concurrent chemoradiotherapy (CCRT) on overall survival and esophageal squamous cell carcinoma (ESCC)-specific survival in patients with ESCC receiving standard CCRT. METHODS: In this propensity score-matching cohort study, we used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to investigate the effects of statin use during the period of CCRT on overall survival and ESCC-specific survival. RESULTS: Statin use during the period of CCRT was found to be a considerable and independent prognostic factor for overall survival and ESCC-specific survival. The adjusted hazard ratio (aHR) for all-cause mortality in the statin group compared with that of the non-statin group was 0.65 (95% confidence interval: 0.51-0.84, p = 0.0009). The aHR for ESCC-specific mortality in the statin group compared with that of the non-statin group was 0.63 (95% confidence interval: 0.47-0.84, p = 0.0016). The use of hydrophilic statins such as rosuvastatin and pravastatin was associated with the greatest survival benefits. A dose-response relationship was also found, with higher cumulative defined daily doses and higher daily intensity of statin use associated with lower mortality. CONCLUSIONS: This study is the first to reveal that statin use during the period of CCRT for ESCC is associated with improvement in overall survival and ESCC-specific survival. In addition, we found that use of rosuvastatin, pravastatin, and simvastatin was associated with better survival outcomes for patients with ESCC receiving CCRT. Furthermore, we found a dose-response relationship of statin use associated with lower ESCC-specific mortality.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/terapia , Estudos de Coortes , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pontuação de Propensão , Rosuvastatina Cálcica/uso terapêutico , Pravastatina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quimiorradioterapia/efeitos adversos
14.
Biomedicines ; 11(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36831114

RESUMO

Esophageal cancer is a common and aggressive cancer, with a five-year survival rate of approximately 20%. Therefore, identifying safe and effective medications that can reduce the risk of esophageal cancer is of great importance. OBJECTIVE: To examine the association between H1-antihistamines (AHs) use and the incidence of esophageal squamous cell carcinoma (ESCC) in a head-to-head propensity score matching (PSM) comparative study. DESIGN: Retrospective cohort study. SETTING: Nationwide population-based study in Taiwan. PARTICIPANTS: 1289,526 adults from the National Health Insurance Research Database from 2008 to 2018. EXPOSURES: AH use. MAIN OUTCOMES AND MEASURES: Incidence rates (IRs), incidence rate ratios (IRRs), and adjusted hazard ratios (aHRs) of ESCC in AH users compared with nonusers. RESULTS: AH users had a significantly higher IR of ESCC than nonusers (1.47 vs. 1.36 per 100,000 person-years). The IRR (95% CI) for ESCC was 1.18 (1.08-1.28) in AH users compared with nonusers. After adjustment for age, sex, income levels, urbanization, cigarettes smoking, alcoholic related diseases, comorbidities, medication use, and Charlson Comorbidity Index scores, the aHR (95% CI) for ESCC was 1.22 (1.12-1.33) in AH users compared with nonusers. A dose-response relationship was also observed, with aHRs for AH use at 28-182, 183-488, 489-1043, and >1043 cumulative defined daily doses (cDDDs) of 1.12, 1.20, 1.25, and 1.37, respectively, compared with <28 cDDDs. CONCLUSIONS AND RELEVANCE: Our study found a significant association between AH use and the increased risk of ESCC, with a dose-response relationship. This study suggests that AH use may increase the risk of ESCC, especially at high doses, and highlights the importance of caution when prescribing AHs.

15.
Cancer Lett ; 561: 216140, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36948240

RESUMO

Met proto-oncogene exon 14 skipping (METex14) mutations are targetable driver genes in approximately 3% of non-small-cell lung cancers (NSCLCs). Ensartinib, a type Ia MET inhibitor, is a multi-kinase inhibitor that has been approved for ALK-positive NSCLCs. Ensartinib was administered for compassionate use (cohort 1) and in a phase II clinical trial (cohort 2) to patients with METex14 mutant NSCLCs, with ORR as a primary endpoint. Molecular simulation was conducted to evaluate ensartinib c-MET interaction, and cell lines, patient-derived organoids (PDOs), and xenograft models were used to test the effectiveness of ensartinib. Among 29 evaluable patients, the ORR and DCR of ensartinib were 67% and 94% in cohort 1, and 73% and 91% in cohort 2. The median DoR was 6.8 months and median PFS was 6.1 months in the total population. Rash was the most common drug-related adverse event, and peripheral edema of any grade was reported in only 9% patients. Molecular simulations indicated favorable binding of ensartinib to c-MET. The kinase assay demonstrated an IC50 of 7.9 nM of ensartinib against METex14 protein. In vitro, Hs746T (METex14 mutation) and EBC-1 (MET amplification) cells were sensitive to ensartinib, with IC50 values of 31 and 44 nM, respectively. Ensartinib exhibited comparable inhibitory effects on cell migration as crizotinib and tepotinib in both cell types. In vivo, ensartinib suppressed the growth of Hs746T cells. Ensartinib also potently inhibited the viability of PDOs. Overall, Ensartinib exhibited substantial antitumor effects against METex14 mutant NSCLCs in preclinical and clinical trials, with relatively low peripheral edema rates.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Éxons , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , Animais
16.
J Chem Phys ; 136(2): 024701, 2012 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-22260604

RESUMO

C(60) molecules assemble into close packing layer under the domination of the intermolecular interaction when deposited onto Pt(111)-supported FeO layer kept at 400 K. From corresponding high resolution scanning tunneling microscopy (STM) image, a kind of C(60) molecular orientational ordering stabilized by the intermolecular interaction is revealed as C(60)/FeO(111)-(√133 × âˆš133) R17.5° structure and determined from the commensurability between the C(60) nearest-neighbor distance and the lattice of the underlying oxygen layer. Moreover, due to the inhomogeneously distributed work function of the underlying FeO layer, the C(60) molecular electronic state is periodically modulated resulting in a bright-dim STM contrast. In addition, one coincidence lattice ordering is determined as 8 × 8 superstructure with respect to the C(60) primitive cell, which overlays a 3 × 3 moiré cell of the underlying FeO layer.


Assuntos
Compostos Férricos/química , Fulerenos/química , Platina/química , Propriedades de Superfície
17.
J Chem Phys ; 136(14): 144707, 2012 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-22502543

RESUMO

The structures and orientations of cobalt phthalocyanine (CoPc) adsorbed on Sb(111) were investigated by low-temperature scanning tunneling microscope. We found that at the initial coverage molecular domains formed both on the terraces and at the vicinity of step edges that were saturated by molecular chains in advance. With the increasing of molecular coverage, the alternately arranged molecular rows of CoPc adsorbed on the bridge sites of Sb(111) and the orientations of them were rotated by 14° ± 2° with respect to the [-101] direction. At the coverage above one monolayer, the molecules of the second layer were assembled along the directions of the underlying molecular rows and showed similar configurations. Consequently, the second-layer CoPc molecules interacted with neighboring molecules via π orbitals, resulting in the observation of overlapped molecular orbitals.

18.
Artigo em Inglês | MEDLINE | ID: mdl-22259350

RESUMO

In the title compound, (C(14)H(16)N(4))(2)[Mo(8)O(26)], the ß-octa-molybdate anion is centrosymmetric. N-H⋯O hydrogen bonds link the diimidazolium cations and the polyoxidoanions into a chain structure along [100]. π-π inter-actions between the imidazole rings and between the imidazole and benzene rings [centroid-centroid distances = 3.611 (2) and 3.689 (3) Å, respectively] connect the chains.

19.
Artigo em Inglês | MEDLINE | ID: mdl-22259504

RESUMO

In the title compound, C(12)H(6)F(2)N(2)O(2), the 2,2-difluoro-1,3-benzodioxole ring system is approximately planar [maximum deviation = 0.012 (2) Å] and its mean plane is twisted with respect to the pyrrole ring, making a dihedral angle of 2.51 (9)°. In the crystal, N-H⋯N hydrogen bonds link the mol-ecules into chains running along the a axis. π-π stacking is also observed between parallel benzene rings of adjacent mol-ecules, the centroid-centroid distance being 3.7527 (13) Å.

20.
Artigo em Inglês | MEDLINE | ID: mdl-22259505

RESUMO

In the title compound, C(2)H(10)N(2) (2+)·C(11)H(10)O(6) (2-), the two acetate groups of the cation form dihedral angles of 74.2 (4) and 63.9 (5)° with the central benzene ring. In the crystal, N-H⋯O hydrogen bonds link the cations and anions into layers parallel to the ab plane.

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