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1.
J Esthet Restor Dent ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38837612

RESUMEN

OBJECTIVE: This article aims to showcase the implementation of a digital workflow in addressing a case of multifactorial excessive gingival display in a patient with high esthetic demands, incorporating both surgical and restorative interventions in a single session. CLINICAL CONSIDERATIONS: A 28-year-old female patient presented with excessive gingival display, attributed to a combination of short teeth due to altered passive eruption, lip hyperactivity, and a sub-nasal depression that lodged the upper lip during spontaneous smiling. The multidisciplinary treatment strategy encompassed surgical crown lengthening, the placement of a biovolume in the maxillary concavity, and the rehabilitation of the six anterior teeth with direct composite resin, all done in a single session. Smilecloud Biometrics was used to digitally plan the smile, and the final wax-up/mock-up was approved by the patient prior to any irreversible procedure. A digital planning center (GuiderLab) enabled the materialization of the virtual planning and the printing of the periodontal surgical guide, the biovolume, and the resin layering guides for the restorative technique. CONCLUSIONS: Adopting a digital workflow in multidisciplinary cases with excessive gingival display leads to predictable and more expedited outcomes, ensuring a favorable result between soft and hard tissues. CLINICAL SIGNIFICANCE: Excessive gingival display is a condition with multifactorial etiologies, including dentoalveolar, periodontal, skeletal, or muscular origins, or a combination of these factors. The diagnoses of altered passive eruption and a hypermobile upper lip are common in daily clinical practice and can be successfully managed through surgical crown lengthening and filling of the maxillary concavity, respectively. To achieve the desired outcome, restorative procedures often complement these surgical interventions.

2.
J Esthet Restor Dent ; 36(5): 746-760, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38130045

RESUMEN

OBJECTIVE: This scoping review aims to assess the influence of air abrasion with aluminum oxide and bioactive glass on dentin bond strength. MATERIALS AND METHODS: An electronic search was conducted in three databases (PubMed, Cochrane Library, and Embase), on March 3rd, 2023, with previously identified MeSH Terms. A total of 1023 records were screened. Exclusion criteria include primary teeth, air abrasion of a substrate other than sound dentin, use of particles apart from aluminum oxide or bioactive glass, and studies in which bond strength was not assessed. RESULTS: Out of the 1023 records, title and abstract screening resulted in the exclusion of 895 and 67 studies, respectively, while full-text analysis excluded another 25 articles. In addition, 5 records were not included, as full texts could not be obtained after requesting the authors. Two cross-references were added. Thus, 33 studies were included in this review. It is important to emphasize the absence of standardization of air abrasion parameters. According to 63.6% of the studies, air abrasion does not influence dentin bond strength. Moreover, 30.3% suggest improving bonding performance, and 6.1% advocate a decrease. CONCLUSIONS: Air abrasion with aluminum oxide does not enhance or impair dentin bond strength. The available data on bioactive glass are limited, which hinders conclusive insights. CLINICAL SIGNIFICANCE: Dentin air abrasion is a widely applied technique nowadays, with numerous clinical applications. Despite the widespread adoption of this procedure, its potential impact on bonding performance requires a thorough analysis of the existing literature.

3.
Int J Cancer ; 150(5): 868-880, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34751446

RESUMEN

Surgical resection with lymphadenectomy and perioperative chemotherapy is the universal mainstay for curative treatment of gastric cancer (GC) patients with locoregional disease. However, GC survival remains asymmetric in West- and East-world regions. We hypothesize that this asymmetry derives from differential clinical management. Therefore, we collected chemo-naïve GC patients from Portugal and South Korea to explore specific immunophenotypic profiles related to disease aggressiveness and clinicopathological factors potentially explaining associated overall survival (OS) differences. Clinicopathological and survival data were collected from chemo-naïve surgical cohorts from Portugal (West-Europe cohort [WE-C]; n = 170) and South Korea (East-Asia cohort [EA-C]; n = 367) and correlated with immunohistochemical expression profiles of E-cadherin and CD44v6 obtained from consecutive tissue microarrays sections. Survival analysis revealed a subset of 12.4% of WE-C patients, whose tumors concomitantly express E-cadherin_abnormal and CD44v6_very high, displaying extremely poor OS, even at TNM stages I and II. These WE-C stage-I and -II patients tumors were particularly aggressive compared to all others, invading deeper into the gastric wall (P = .032) and more often permeating the vasculature (P = .018) and nerves (P = .009). A similar immunophenotypic profile was found in 11.9% of EA-C patients, but unrelated to survival. Tumours, from stage-I and -II EA-C patients, that display both biomarkers, also permeated more lymphatic vessels (P = .003), promoting lymph node (LN) metastasis (P = .019), being diagnosed on average 8 years earlier and submitted to more extensive LN dissection than WE-C. Concomitant E-cadherin_abnormal/CD44v6_very-high expression predicts aggressiveness and poor survival of stage-I and -II GC submitted to conservative lymphadenectomy.


Asunto(s)
Biomarcadores de Tumor/análisis , Cadherinas/análisis , Receptores de Hialuranos/análisis , Neoplasias Gástricas/mortalidad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía
4.
Environ Res ; 211: 113090, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35278468

RESUMEN

Artisanal gold (Au) mining may have increased the concentrations of rare earth elements (REEs) in the Serra Pelada mine (southeastern Amazon, Brazil), which has not been evaluated so far. The objectives of this study were to determine the concentrations of cerium (Ce), lanthanum (La), scandium (Sc), and yttrium (Y) in the surroundings of the Serra Pelada mine, as well as the environmental risks associated with these elements. Therefore, 27 samples were collected in agricultural, forest, mining, and urban areas, and submitted to chemical and particle size characterization. The concentrations of REEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS) and used to estimate pollution indices and environmental risks of the studied elements. All REEs had higher levels in the anthropized areas when compared to the forest area, except Sc in the mining and urban areas. Pollution load indices revealed that all areas are contaminated (>1) by the combined effect of REEs, especially the agricultural areas (index of 2.3). The element of greatest enrichment in the studied areas was Y, with enrichment factors of 18.2, 39.0, and 44.4 in the urban, agriculture, and mining areas, respectively. However, the potential ecological risk indices were low (<150) in all areas, indicating that there are no current environmental risks by the studied REEs.


Asunto(s)
Oro , Metales de Tierras Raras , Monitoreo del Ambiente/métodos , Contaminación Ambiental/análisis , Oro/análisis , Metales de Tierras Raras/análisis , Minería
5.
BMC Public Health ; 21(Suppl 2): 2336, 2022 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-35818044

RESUMEN

BACKGROUND: Falls are associated with cognitive and physical function deterioration. Attention decline, inaccurate affordance perception, and balance impairment are considered to be risk factors for falls. Furthermore, few studies have reported psychomotor intervention as a fall prevention program. This study aimed to investigate the effects of two multimodal programs on attention, perceptual and stepping-forward boundaries, and balance in community-dwelling older adults at risk of falling. METHODS: Fifty-one community-dwelling older adults were recruited to participate in a 24-week randomized controlled trial. Participants (75.4 ± 5.6 years) were randomly assigned to one of three groups: the 1) multimodal psychomotor program [EG1], 2) combined program (multimodal psychomotor program + whole-body vibration program) [EG2], and 3) control group. Participants were assessed at baseline, at post-intervention, and after a 12-week no-intervention follow-up period. RESULTS: The within-group comparisons showed significant improvements in attention and balance in EG1 and EG2 after the intervention (p <  0.05). The magnitudes of the treatment effects were similar in both EGs, ranging from medium to large. Decreases in the fall rate were also observed in EG1 (- 44.2%) and EG2 (- 63.0%) (p <  0.05). During the follow-up period, these improvements in attention were maintained, while those in balance were reversed in both EGs. No significant differences between groups were found. CONCLUSIONS: These study results suggest that both multimodal exercise programs were effective for fall prevention and were well tolerated by the participants. Specifically, EG1 and EG2 showed identical improvements in attention, and EG2 presented a slightly larger enhancement in balance and a larger decrease in the fall rate. Our findings demonstrate the benefits of maintaining the psychomotor intervention program by itself or in combination with the whole-body vibration program to prevent cognitive and physical function deterioration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03446352 . Date of registration: February 26, 2018.


Asunto(s)
Vida Independiente , Equilibrio Postural , Anciano , Atención , Terapia por Ejercicio/métodos , Humanos , Percepción
6.
Lasers Med Sci ; 38(1): 23, 2022 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-36564660

RESUMEN

The objective of this study is to clarify whether PBM for measures reduction can cause significant changes in the lipid profile. This is an integrative review and only original articles, both in vivo and clinical trials, that were published between 2010 and 2022 were selected. The article references were also analyzed to identify additional studies. A total of 15 articles were critically analyzed. The wavelength used ranged from 532 nm (green) to 956 nm (near infrared), and many authors failed to describe dosimetric parameters properly, as well as other important characteristics for the reproducibility of those found. Although it is not fully clear about the PBM interference level on the lipid profile, in general, there was no significant difference in lipid parameters when PBM was used alone, and when associated with techniques that promote beta-oxidation, there was an improvement in these biochemical variables. PBM use for localized fat reduction do not affect lipid serum levels. Clinical trials using standardized parameters are crucial to obtain more reliable results.


Asunto(s)
Terapia por Luz de Baja Intensidad , Reproducibilidad de los Resultados , Terapia por Luz de Baja Intensidad/métodos , Lípidos
7.
Geriatr Nurs ; 47: 135-144, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35914490

RESUMEN

This study aimed to design a dynamic performance-exposure algorithm for falling risk assessment and prevention of falls in community-dwelling older adults. It involved a cross-sectional and follow-up survey assessing retrospective and prospective falls and respective performance-related, exposure and performance-exposure risk factors. In total, 500 Portuguese community-dwelling adults participated. Data modelling showed significant (p<0.05) relationships between the above risk factors and selected nine key ordered outcomes explaining falls to include in the algorithm: previous falls; health conditions; balance; lower strength; perceiving action boundaries; fat mass; environmental hazards; rest periods; and physical activity. Respective high-, moderate- and low-risk cutoffs were established. The results demonstrated a dynamic relationship between older adults' performance capacity and the exposure to fall opportunity, counterbalanced by the action boundary perception, supporting the build algorithm's conceptual framework. Fall prevention measures should consider the factors contributing most to the individual risk of falling and their distance from low-risk safe values.


Asunto(s)
Vida Independiente , Equilibrio Postural , Anciano , Algoritmos , Estudios Transversales , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
8.
Funct Integr Genomics ; 21(1): 73-99, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33404914

RESUMEN

Lignin is the main component of secondary cell walls and is essential for plant development and defense. However, lignin is recognized as a major recalcitrant factor for efficiency of industrial biomass processing. Genes involved in general phenylpropanoid and monolignol-specific metabolism in sugarcane have been previously analyzed at the transcriptomic level. Nevertheless, the number of genes identified in this species is still very low. The recently released sugarcane genome sequence has allowed the genome-wide characterization of the 11 gene families involved in the monolignol biosynthesis branch of the phenylpropanoid pathway. After an exhaustive analysis of sugarcane genomes, 438 haplotypes derived from 175 candidate genes from Saccharum spontaneum and 144 from Saccharum hybrid R570 were identified as associated with this biosynthetic route. The phylogenetic analyses, combined with the search for protein conserved residues involved in the catalytic activity of the encoded enzymes, were employed to identify the family members potentially involved in developmental lignification. Accordingly, 15 candidates were identified as bona fide lignin biosynthesis genes: PTAL1, PAL2, C4H4, 4CL1, HCT1, HCT2, C3'H1, C3'H2, CCoAOMT1, COMT1, F5H1, CCR1, CCR2, CAD2, and CAD7. For this core set of lignin biosynthetic genes, we searched for the chromosomal location, the gene expression pattern, the promoter cis-acting elements, and microRNA targets. Altogether, our results present a comprehensive characterization of sugarcane general phenylpropanoid and monolignol-specific genes, providing the basis for further functional studies focusing on lignin biosynthesis manipulation and biotechnological strategies to improve sugarcane biomass utilization.


Asunto(s)
Genes de Plantas , Lignina/biosíntesis , Saccharum/genética , Haplotipos , Lignina/genética , Fenilpropionatos/metabolismo , Filogenia , Polimorfismo Genético , Saccharum/clasificación , Saccharum/metabolismo
9.
J Biochem Mol Toxicol ; 35(3): e22663, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33125183

RESUMEN

Imidazo[1,2-a]pyridines (IP) and organoselenium compounds have been widely exploited in medicinal chemistry due to their pharmacological activities. Hepatocellular carcinoma (HCC) has few treatment options, and unfortunately, the prognosis is poor. Thus, the development of novel therapeutic drugs is urgent. The present study aimed at evaluating the antitumor mechanism of selenylated IP against HepG2 cells and in vivo. The selenylated IP named IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine) showed high cytotoxicity against HepG2 cells (half-maximal inhibitory concentration [IC50 ] = 0.03 µM) and selectivity for this tumor cell line. At nontoxic concentration, IP-Se-06 decreased the protein levels of Bcl-xL and increased the levels of p53, leading to inhibition of cell proliferation and apoptosis. This compound decreased the level of extracellular signal-regulated kinase 1/2 protein and changed the levels of proteins involved in the drive of the cell cycle, tumor growth, and survival (cyclin B1, cyclin-dependent kinase 2). In addition, IP-Se-06 decreased the number of cells in the S phase. In addition, IP-Se-06 led to increased generation of reactive oxygen species, changed antioxidant defenses, and caused DNA fragmentation. Finally, IP-Se-06 significantly inhibited the growth of Ehrlich ascites tumors in mice, increased survival time, and inhibited angiogenesis. Therefore, IP-Se-06 may be an important compound regarding the development of a therapeutic drug for HCC treatment.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Organoselenio/farmacología , Estrés Oxidativo/efectos de los fármacos , Piridinas/farmacología , Animales , Antineoplásicos/química , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Compuestos de Organoselenio/química , Piridinas/química , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Curr Microbiol ; 78(7): 2682-2694, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34013423

RESUMEN

The aim of this study is to evaluate the effect of different thermal pretreatments of the inoculum on the diversity of the microbial community producing hydrogen from sugarcane vinasse. High-throughput sequencing of the 16S and 18S rRNA genes was performed. The reactor samples were also selected for the isolation of strict anaerobes. Decreased microbial diversity was observed with increasing pretreatment temperatures, with Firmicutes predominating: 90% to 97%. The highest abundance of Staphylococcus (7.9%) was found in pretreatment at 120 °C / 20 min at pH 6. The fungal analysis revealed a high prevalence of Candida (47%), Agaricomycetes, Pezizomycotina and Aspergillus in assays with higher H2 production (90° C / 10 min at pH 6). Three species of Clostridium were isolated: C. bifermentans, C. saccharoperbutylacetonicum and C. saccharobutylicum. The isolates were tested separately and in co-cultures for the production of hydrogen. Hydrogen-producing capacity by co-culture of Clostridium species was increased by 18%. Knowing microorganisms and understanding the interaction between eukaryotes and prokaryotes is essential to obtain strategies for biotransformation of vinasse for the production of bioenergy.


Asunto(s)
Saccharum , Bacterias Anaerobias , Eucariontes , Hidrógeno , Temperatura
11.
BMC Public Health ; 21(Suppl 2): 977, 2021 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-34758785

RESUMEN

BACKGROUND: Fall risk assessment and determination of older adults' individual risk profiles are crucial elements in fall prevention. As such, it is essential to establish cutoffs and reference values for high and low risk according to key risk factor outcomes. This study main objective was to determine the key physical fitness, body composition, physical activity, health condition and environmental hazard risk outcome cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults. METHODS: Five-hundred community-dwelling Portuguese older adults (72.2 ± 5.4 years) were assessed for falls, physical fitness, body composition, physical (in) activity, number of health conditions and environmental hazards, and sociodemographic characteristics. RESULTS: The established key outcomes and respective cutoffs and reference values used for fall risk stratification were multidimensional balance (low risk: score > 33, moderate risk: score 32-33, high risk: score 30-31, and very high: score < 30); lean body mass (low risk: > 44 kg, moderate risk: 42-44 kg, high risk: 39-41 kg, and very high: < 39 kg); fat body mass (low risk: < 37%, moderate risk: 37-38%, high risk: 39-42%, and very high: > 42%); total physical activity (low risk: > 2800 Met-min/wk., moderate risk: 2300-2800 Met-min/wk., high risk: 1900-2300 Met-min/wk., and very high: < 1900 Met-min/wk); rest period weekdays (low risk: < 4 h/day, moderate risk: 4-4.4 h/day, high risk: 4.5-5 h/day, and very high: > 5 h/day); health conditions (low risk: n < 3, moderate risk: n = 3, high risk: n = 4-5, and very high: n > 5); and environmental hazards (low risk: n < 5, moderate risk: n = 5, high risk: n = 6-8, and very high: n > 8). CONCLUSIONS: Assessment of community-dwelling older adults' fall risk should focus on the above outcomes to establish individual older adults' fall risk profiles. Moreover, the design of fall prevention interventions should manage a person's identified risks and take into account the determined cutoffs and respective interval values for fall risk stratification.


Asunto(s)
Accidentes por Caídas , Vida Independiente , Accidentes por Caídas/prevención & control , Anciano , Composición Corporal , Ejercicio Físico , Humanos , Aptitud Física , Valores de Referencia , Medición de Riesgo
12.
Vet Dermatol ; 32(5): 438-e117, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34240488

RESUMEN

BACKGROUND: Dermatobia hominis (D. hominis) is a botfly that causes furuncular myiasis in several species of domestic and wild animals. However, reports of feline infestation by larvae of this dipteran are rare. OBJECTIVE: To report the natural occurrence of furuncular myiasis caused by D. hominis in five cats and the efficacy of topical fluralaner for its treatment. ANIMALS: Five adult mixed-breed cats (four males, one female) were diagnosed and treated, all living in the state of Rio de Janeiro, Brazil. RESULTS: The cats were treated with topical fluralaner. After this treatment, the larvae were dead after 24 h in three cats and after 48 h in two. There was spontaneous expulsion of larvae in two cats, and it was necessary to perform manual expression for removal of dead larvae in the other three cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Dermatobia hominis can cause furuncular myiasis in cats, although this appears to be less common than in other animal species. Topical fluralaner proved to be effective in the treatment of this parasitic disease.


Asunto(s)
Enfermedades de los Gatos , Dípteros , Miasis , Animales , Brasil , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Femenino , Isoxazoles , Larva , Masculino , Miasis/tratamiento farmacológico , Miasis/veterinaria
13.
Am J Dent ; 33(1): 29-32, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32056412

RESUMEN

PURPOSE: To assess the association between obstructive sleep apnea (OSA) and enamel cracks. METHODS: 219 patients were included. Separate operators assessed the sleep component of the study and the visual evaluation of the enamel cracks. Anthropometric data were also obtained. RESULTS: Patients with slightly marked (superficial) enamel cracks had a significantly lower apnea-hypoapnea index (AHI) than the patients with moderately-to-severely marked (deep) craze lines. The frequency of patients with moderately-to-severely marked craze lines increased with the severity of OSA. Spearman's correlation indicated the presence of a statistically significant association between the severity of enamel crack and the severity of OSA. Multiple regression analysis indicated that age, sex, body mass index and OSA significantly affected the enamel cracks. Compared to patients with slightly marked craze lines, those with moderate-to-severe craze lines are higher aged males, with a higher body mass index and increased severity of OSA. CLINICAL SIGNIFICANCE: The presence of moderate to severe enamel cracks may alert the clinician to the need to diagnose obstructive sleep apnea.


Asunto(s)
Apnea Obstructiva del Sueño , Índice de Masa Corporal , Esmalte Dental , Humanos , Masculino , Polisomnografía
14.
Gastric Cancer ; 22(1): 77-90, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29779068

RESUMEN

BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations. CD3+ and CD8+ T-cell densities were calculated by digital analysis. Fifty-four non-GCLSs were used as control group. RESULTS: GCLSs displayed distinctive clinicopathological features, such as lower pTNM stage (p = 0.02) and better overall survival (p = 0.01). EBV+ or MSI-high phenotype was found in 66.7 and 16.7% cases, respectively. GCLSs harbored a cytotoxic T-cell-inflamed profile, particularly at the invasive front of tumors (p < 0.01) and in EBV+ cases (p = 0.01). EBV+ GCLSs, when compared to EBV- GCLSs, showed higher mRNA expression of genes related to Th1/cytotoxic and immunosuppressive biomarkers. PD-L1 protein expression, observed in neoplastic and immune stromal cells (33.3 and 91.7%, respectively), and PD-L1 amplification (18.8%) were restricted to EBV+/MSI-high tumors and correlated with high values of PD-L1 mRNA expression. CONCLUSIONS: This study shows that GCLS has a distinctive clinico-pathological and molecular profile. Furthermore, through an in-depth study of tumor immune microenvironment-by digital analysis and mRNA expression profiling-it highlights the role of EBV infection in promoting an inflamed tumor microenvironment, with putative therapeutic implications.


Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Gástricas/patología , Microambiente Tumoral/inmunología , Adulto , Anciano , Antígeno B7-H1/biosíntesis , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Herpesvirus Humano 4 , Humanos , Inmunofenotipificación , Inflamación/genética , Inflamación/inmunología , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Transcriptoma , Microambiente Tumoral/genética
15.
Biochem Biophys Res Commun ; 503(3): 1291-1297, 2018 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-30017191

RESUMEN

A novel series of selenylated imidazo[1,2-a]pyridines were designed and synthesized with a view to a promising activity against breast cancer cell. The compounds, 7-methyl-3-(naphthalene-1-ylselanyl)-2-phenylimidazo[1,2-a]pyridine, named IP-Se-05, and 3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazo[1,2-a]pyridine, named IP-Se-06, showed high cytotoxicity for MCF-7 cells (IC50 = 26.0 µM and 12.5 µM, respectively). Both the compounds inhibited the cell proliferation and caused decrease in the number of cells in the G2/M phase of cell cycle. IP-Se-05 and IP-Se-06 were also evaluated for effects on CT-DNA and DNA of MCF-7 cells. The compounds intercalated into CT-DNA and both treatments caused cleavage of DNA in cells. In addition, the compounds induced cell death by apoptosis. However, the presence of (2-methoxyphenyl) selenyl moiety at the imidazo[1,2-a]pyridine (IP-Se-06) appears to have a better antitumor effect with higher cytotoxicity at a lower concentration and caused less necrosis. Overall, the current study established IP-Se-06 more than IP-Se-05 as a potential prototype compound to be employed as an antiproliferative agent for the treatment of breast cancer.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , División del ADN/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirimidinas/farmacología , Antineoplásicos/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Estructura Molecular , Pirimidinas/química , Relación Estructura-Actividad , Células Tumorales Cultivadas
16.
Pathobiology ; 85(1-2): 50-63, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28618420

RESUMEN

Gastric cancer (GC) represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still the third leading cause of cancer mortality worldwide, with more than 720,000 estimated deaths in 2012. Overall survival for advanced disease is about 1 year, a dismal prognosis that is partly due to the high levels of biological heterogeneity found in GC. Indeed, GC is a highly heterogeneous disease from morphological and molecular standpoints. The numerous histological and molecular classifications currently available reflect such heterogeneity. Although recent high-throughput studies cluster the molecular data obtained into subgroups with clinical relevance, we still need a practical, prognostic, and predictive classification system, integrating morphological and molecular features, towards the identification of novel therapeutic targets. It is noteworthy that GC heterogeneity encompasses not only interpatient variability (intertumour heterogeneity), but also variations within the same tumour (intratumour heterogeneity). The latter encompasses spatial heterogeneity (in different tumour areas) and temporal heterogeneity (along progression from primary to recurrent and/or metastatic disease). In this review, we analyse the morphological, immunophenotypic, and molecular heterogeneity in GC as the basis for a better understanding of the disease, and discuss the practical implications for diagnostic pathology, prognostic evaluation, and precision therapy.


Asunto(s)
Biomarcadores de Tumor/genética , Heterogeneidad Genética , Neoplasias Gástricas/clasificación , Progresión de la Enfermedad , Humanos , Medicina de Precisión , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología
17.
Int J Cancer ; 141(7): 1478-1489, 2017 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-28639285

RESUMEN

Gastric cancer (GC) is the 3rd deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2-3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC. Using mass spectrometry analysis, the lysine residues in the trastuzumab structure most prone for porphyrin conjugation were mapped. The in vitro data demonstrates that Trast:Porph specifically binds to HER2-positive cells, accumulates intracellularly, co-localizes with lysosomal marker LAMP1, and induces massive HER2-positive cell death upon cellular irradiation. The high selectivity and cytotoxicity of Trast:Porph based photoimmunotherapy is confirmed in vivo in comparison with trastuzumab alone, using nude mice xenografted with a HER2-positive GC cell line. In the setting of human disease, these data suggest that repetitive cycles of Trast:Porph photoimmunotherapy may be used as an improved treatment strategy in HER2-positive GC patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Muerte Celular , Inmunoterapia/métodos , Fotoquimioterapia/métodos , Porfirinas/uso terapéutico , Receptor ErbB-2 , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Lisina/química , Proteínas de Membrana de los Lisosomas/farmacocinética , Masculino , Espectrometría de Masas , Ratones Desnudos , Porfirinas/química , Porfirinas/farmacocinética , Distribución Aleatoria , Neoplasias Gástricas/metabolismo , Trastuzumab/química , Trastuzumab/farmacocinética , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Analyst ; 142(2): 375-379, 2017 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-27996066

RESUMEN

Dielectrophoresis (DEP) is the electrokinetic movement of non-charged particles when they are subjected to a non-uniform electric field. This is a growing area of research, which can be used for trapping, concentrating and separating different particles. Some work has been reported with the intention of trapping metal particles to optimize the surface enhanced Raman spectroscopy (SERS) effect. In this paper, we use DEP with insulating structures (iDEP) to generate a non-uniform electric field for trapping gold nanoparticles (AuNP). The system was coupled to a Raman spectrometer for the detection of Crystal Violet by utilizing the SERS effect.

19.
Respirology ; 22(2): 378-385, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27623414

RESUMEN

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea is a prevalent and considerably underdiagnosed disease. The development of cost-effective, home-based, automatic diagnostic devices to improve the diagnosis accessibility is therefore essential. METHODS: In this study, a new portable polygraph (BTI-APNiA) was used to validate automatic scoring. This five-channel device records respiratory flow, oxygen saturation, heart rate, body position and snoring. The validation was performed in two phases. In the first phase, manual and automatic scorings of a new respiratory polygraphy (RP) device (BTI-APNiA) were compared. In the second phase, automatic analysis performed with BTI-APNiA was compared with manual scoring of a validated RP device (Embletta Gold). RESULTS: Phase I was completed by 424 patients (50.5% males, 52.2 ± 12.4 years, BMI of 25.4 ± 4.8 kg/m2 and Epworth Sleepiness Scale score of 8.0 ± 4.0). Manual and automatic analysis resulted in an apnoea-hypopnoea index (AHI) of 13.7 ± 12.7 and 14.0 ± 12.5 (P > 0.05), respectively. The interclass correlation coefficient (ICC) was 0.99 (P < 0.001). During Phase II, 28 patients were evaluated (72.0% men, 49.1 ± 10.9 years, BMI of 27.1 ± 4.2 kg/m2 and Epworth Sleepiness Scale score of 7.5 ± 4.2). Manual analysis of Embletta Gold recordings indicated an AHI of 12.3 ± 14.0, while automatic analysis of the BTI-APNiA was 13.4 ± 14.7 (P > 0.05). The ICC was 0.68 (P < 0.01). CONCLUSION: The automatic analysis of the BTI-APNiA is as accurate as manual analysis of AHI. This automatic analysis compared well with the manual analysis of a validated RP device (Embletta Gold).


Asunto(s)
Polisomnografía , Apnea Obstructiva del Sueño , Adulto , Anciano , Diagnóstico por Computador , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Aplicaciones Móviles , Consumo de Oxígeno , Sistemas de Atención de Punto , Polisomnografía/instrumentación , Polisomnografía/métodos , Reproducibilidad de los Resultados , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , España
20.
Int J Cancer ; 134(6): 1270-8, 2014 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-24105655

RESUMEN

Tumour drug resistance is a major issue in the management of lung cancer patients as almost all lung tumours are either intrinsically resistant or quickly develop acquired resistance to chemotherapeutic drugs. Cancer drug resistance has recently been linked, at least in part, to the existence of cancer stem-like cells (CSLCs), a small sub-population of cells within the tumour that possess stem-like properties. CSLCs are often isolated by fluorescence activated cell sorting (FACS) according to the expression of certain stem-like cell membrane markers. Conflicting results regarding the specificity of particular stem cell surface markers for isolating CSLCs have, however, been recently reported. Therefore, alternative strategies enabling the identification and study of CSLCs should be considered, particularly in tumour types where appropriate stem cell markers are not well established and validated, like in lung cancer. In this article, we review data indicating therapy-selection as a valid approach for putative lung CSLCs enrichment. We believe that this strategy would be determinant for correctly assessing and characterising the sub-populations of CSLCs that are able to survive chemo or radiotherapy regimens and, at the same time, also have the ability to recapitulate and sustain tumour growth. Using therapy-induced enrichment of CSLCs may, therefore, prove to be an extremely useful method for studying CSLCs and provide new clues regarding potential therapeutic targets for their efficient elimination, which will undoubtedly play a decisive role in improving lung cancer patients' survival.


Asunto(s)
Terapia Combinada/efectos adversos , Resistencia a Antineoplásicos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Células Madre Neoplásicas/patología , Animales , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/efectos de la radiación
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