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2.
Water Res ; 264: 122208, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39116611

RESUMEN

Surface water ecosystems are intimately intertwined with anthropogenic activities and have significant public health implications as primary sources of irrigation water in agricultural production. Our extensive metagenomic analysis examined 404 surface water samples from four different geological regions in Chile and Brazil, spanning irrigation canals (n = 135), rivers (n = 121), creeks (n = 74), reservoirs (n = 66), and ponds (n = 8). Overall, 50.25 % of the surface water samples contained at least one of the pathogenic or contaminant bacterial genera (Salmonella: 29.21 %; Listeria: 6.19 %; Escherichia: 35.64 %). Furthermore, a total of 1,582 antimicrobial resistance (AMR) gene clusters encoding resistance to 25 antimicrobial classes were identified, with samples from Brazil exhibiting an elevated AMR burden. Samples from stagnant water sources were characterized by dominant Cyanobacteriota populations, resulting in significantly reduced biodiversity and more uniform community compositions. A significant association between taxonomic composition and the resistome was supported by a Procrustes analysis (p < 0.001). Notably, regional signatures were observed regarding the taxonomic and resistome profiles, as samples from the same region clustered together on both ordinates. Additionally, network analysis illuminated the intricate links between taxonomy and AMR at the contig level. Our deep sequencing efforts not only mapped the microbial landscape but also expanded the genomic catalog with newly characterized metagenome-assembled genomes (MAGs), boosting the classification of reads by 12.85 %. In conclusion, this study underscores the value of metagenomic approaches in surveillance of surface waters, enhancing our understanding of microbial and AMR dynamics with far-reaching public health and ecological ramifications.


Asunto(s)
Metagenómica , Microbiota , Microbiología del Agua , Brasil , Bacterias/genética , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Chile
3.
PLoS Biol ; 22(7): e3002658, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38991106

RESUMEN

Tetrapods (amphibians, reptiles, birds, and mammals) are model systems for global biodiversity science, but continuing data gaps, limited data standardisation, and ongoing flux in taxonomic nomenclature constrain integrative research on this group and potentially cause biased inference. We combined and harmonised taxonomic, spatial, phylogenetic, and attribute data with phylogeny-based multiple imputation to provide a comprehensive data resource (TetrapodTraits 1.0.0) that includes values, predictions, and sources for body size, activity time, micro- and macrohabitat, ecosystem, threat status, biogeography, insularity, environmental preferences, and human influence, for all 33,281 tetrapod species covered in recent fully sampled phylogenies. We assess gaps and biases across taxa and space, finding that shared data missing in attribute values increased with taxon-level completeness and richness across clades. Prediction of missing attribute values using multiple imputation revealed substantial changes in estimated macroecological patterns. These results highlight biases incurred by nonrandom missingness and strategies to best address them. While there is an obvious need for further data collection and updates, our phylogeny-informed database of tetrapod traits can support a more comprehensive representation of tetrapod species and their attributes in ecology, evolution, and conservation research.


Asunto(s)
Biodiversidad , Aves , Mamíferos , Filogenia , Reptiles , Animales , Reptiles/clasificación , Anfibios , Ecosistema , Sesgo , Humanos , Tamaño Corporal
4.
Clin Transl Oncol ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907097

RESUMEN

INTRODUCTION: Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS: From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS: In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION: SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

5.
mBio ; 15(7): e0077724, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38920393

RESUMEN

This study examined the diversity and persistence of Salmonella in the surface waters of agricultural regions of Brazil, Chile, and Mexico. Research groups (three in 2019-2020 and five in 2021-2022) conducted a long-term survey of surface water across 5-8 months annually (n = 30 monthly). On-site, each team filtered 10-L water samples with modified Moore Swabs to capture Salmonella, which were then isolated and identified using conventional microbiological techniques. Salmonella isolates were sequenced on Illumina platforms. Salmonella was present in 1,493/3,291 water samples (45.8%), with varying isolation rates across countries and years. Newport, Infantis, and Typhimurium were the most frequent among the 128 different serovars. Notably, 22 serovars were found in all three countries, representing almost half of the 1,911 different isolates collected. The resistome comprised 72 antimicrobial resistance (AMR) genes and six point mutations in three genes. At least one AMR determinant was observed in 33.8% (646/1,911) of the isolates, of which 47.4% (306/646) were potentially multidrug resistant. Phylogeny based on core genome multilocus sequence typing (cgMLST) showed that most isolates clustered according to sequence type and country of origin. Only 14 cgMLST multi-country clusters were detected among the 275 clusters. However, further analysis confirmed that close genetic relatedness occurred mostly among isolates from the same country, with three exceptions. Interestingly, isolates closely related phylogenetically were recovered over multiple years within the same country, indicating the persistence of certain Salmonella in those areas. In conclusion, surface waters in these regions are consistently contaminated with diverse Salmonella, including strains that persist over time.IMPORTANCESalmonella is a leading foodborne pathogen responsible for millions of illnesses, hospitalizations, and deaths annually. Although Salmonella-contaminated water has now been recognized as an important contamination source in the agrifood chain, there is a lack of knowledge on the global occurrence and diversity of Salmonella in surface water. Moreover, there has been insufficient research on Salmonella in surface waters from Latin American countries that are major producers and exporters of agricultural products. Incorporating genetic profiling of Salmonella isolates from underrepresented regions, such as Latin America, enhances our understanding of the pathogen's ecology, evolution, antimicrobial resistance, and pathogenicity. Moreover, leveraging genomic data derived from pathogens isolated from diverse geographical areas is critical for assessing the potential public health risk posed by the pathogen and expediting investigations of foodborne outbreaks. Ultimately, global efforts contribute significantly to reducing the incidence of foodborne infections.


Asunto(s)
Salmonella , Microbiología del Agua , Brasil/epidemiología , Salmonella/genética , Salmonella/clasificación , Salmonella/aislamiento & purificación , México/epidemiología , Chile/epidemiología , Variación Genética , Filogenia , Genoma Bacteriano , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Genómica , Epidemiología Molecular
6.
Genet Mol Biol ; 47(2): e20230231, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577985

RESUMEN

Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor ß-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2's impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients.

7.
Microbiol Spectr ; 12(5): e0004724, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38546218

RESUMEN

Surface waters are considered ecological habitats where Salmonella enterica can persist and disseminate to fresh produce production systems. This study aimed to explore the genomic profiles of S. enterica serotypes Typhimurium, Newport, and Infantis from surface waters in Chile, Mexico, and Brazil collected between 2019 and 2022. We analyzed the whole genomes of 106 S. Typhimurium, 161 S. Newport, and 113 S. Infantis isolates. Our phylogenetic analysis exhibited distinct groupings of isolates by their respective countries except for a notable case involving a Chilean S. Newport isolate closely related to two Mexican isolates, showing 4 and 13 single nucleotide polymorphisms of difference, respectively. The patterns of the most frequently detected antimicrobial resistance genes varied across countries and serotypes. A strong correlation existed between integron carriage and genotypic multidrug resistance (MDR) across serotypes in Chile and Mexico (R > 0.90, P < 0.01), while integron(s) were not detected in any of the Brazilian isolates. By contrast, we did not identify any strong correlation between plasmid carriage and genotypic MDR across diverse countries and serotypes.IMPORTANCEUnveiling the genomic landscape of S. enterica in Latin American surface waters is pivotal for ensuring public health. This investigation sheds light on the intricate genomic diversity of S. enterica in surface waters across Chile, Mexico, and Brazil. Our research also addresses critical knowledge gaps, pioneering a comprehensive understanding of surface waters as a reservoir for multidrug-resistant S. enterica. By integrating our understanding of integron carriage as biomarkers into broader MDR control strategies, we can also work toward targeted interventions that mitigate the emergence and dissemination of MDR in S. enterica in surface waters. Given its potential implications for food safety, this study emphasizes the critical need for informed policies and collaborative initiatives to address the risks associated with S. enterica in surface waters.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Filogenia , Salmonella enterica , Salmonella typhimurium , Serogrupo , Salmonella enterica/genética , Salmonella enterica/aislamiento & purificación , Salmonella enterica/clasificación , Salmonella enterica/efectos de los fármacos , Brasil , Farmacorresistencia Bacteriana Múltiple/genética , México , Salmonella typhimurium/genética , Salmonella typhimurium/aislamiento & purificación , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/clasificación , Integrones/genética , Genoma Bacteriano , Chile , Genómica , Antibacterianos/farmacología , América Latina , Microbiología del Agua , Polimorfismo de Nucleótido Simple , Plásmidos/genética , Pruebas de Sensibilidad Microbiana
8.
Clin Transl Oncol ; 26(7): 1790-1797, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38431539

RESUMEN

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.


Asunto(s)
Neoplasias Hepáticas , Radiocirugia , Radioterapia de Intensidad Modulada , Humanos , Radiocirugia/métodos , Radiocirugia/efectos adversos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/mortalidad , Masculino , Estudios Prospectivos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto , Radioterapia de Intensidad Modulada/métodos , Supervivencia sin Progresión , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/radioterapia , Neoplasias Colorrectales/mortalidad , Radioterapia Guiada por Imagen , Tasa de Supervivencia
9.
Clin Transl Oncol ; 26(1): 204-213, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37277526

RESUMEN

BACKGROUND: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. MATERIAL AND METHODS: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5-60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. RESULTS: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). CONCLUSIONS: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Hipofraccionamiento de la Dosis de Radiación , Recurrencia Local de Neoplasia/patología , Extremidades/patología , Sarcoma/patología , Terapia Neoadyuvante , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/patología , Resultado del Tratamiento , Estudios Retrospectivos
10.
Clin Transl Oncol ; 25(12): 3395-3404, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37058207

RESUMEN

OBJECTIVE: To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. MATERIALS AND METHODS: Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. RESULTS: From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). CONCLUSIONS: According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.


Asunto(s)
Radiocirugia , Neoplasias de la Columna Vertebral , Masculino , Humanos , Radiocirugia/métodos , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/patología , Recurrencia Local de Neoplasia/etiología , Mama/patología , Dolor/etiología , Estudios Retrospectivos
11.
Clin Transl Oncol ; 24(3): 532-539, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34585316

RESUMEN

BACKGROUND: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. MATERIALS AND METHODS: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. RESULTS: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed. CONCLUSION: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results.


Asunto(s)
Articulaciones de la Mano , Osteoartritis/radioterapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosificación Radioterapéutica , Resultado del Tratamiento
12.
Clin Transl Oncol ; 23(7): 1452-1462, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33433839

RESUMEN

PURPOSE: Conventional post-prostatectomy radiation therapy comprises 6.5-8 weeks of treatment, therefore, hypofractionated and shortened schemes arouse increasing interest. We describe our experience regarding feasibility and clinical outcome of a post-prostatectomy moderate hypofractionated image-guided radiotherapy schedule MATERIALS AND METHODS: From Oct 2015-Mar 2020, 113 patients, median age of 62 years-old (range 45-76) and prostate adenocarcinoma of low risk (30%), intermediate risk (49%) and high risk (21%) were included for adjuvant (34%) or salvage radiation therapy (66%) after radical prostatectomy (RP). All patients underwent radiotherapy with image-guided IMRT/VMAT to a total dose of 62.5 Gy in 2.5 Gy/fraction in 25 fractions. Sixteen patients (14%) received concomitant androgen deprivation therapy. RESULTS: With a median follow-up of 29 months (range 3-60 months) all patients but three are alive. Eleven patients (10%) developed exclusive biochemical relapse while 19 patients (17%) presented macroscopically visible relapse: prostatectomy bed in two patients (2%), pelvic lymph nodes in 13 patients (11.5%) and distant metastases in four patients (4%). The 3 years actuarial rates for OS, bFRS, and DMFS were 99.1, 91.1 and 91.2%, respectively. Acute and late tolerance was satisfactory. Maximal acute genitourinary (AGU) toxicity was G2 in 8% of patients; maximal acute gastrointestinal (AGI) toxicity was G2 in 3.5% of patients; maximal late genitourinary (LGU) toxicity was G3 in 1% of patients and maximal late gastrointestinal (LGI) toxicity was G2 in 2% of patients. There were no cases of severe acute or late toxicity. No relationship was found between acute or late GI/GU adverse effects and dosimetric parameters, age, presence of comorbidities or concomitant treatments. CONCLUSIONS: Hypofractionated radiotherapy (62.5 Gy in 25 2.5 Gy fractions) is feasible and well tolerated with low complication rates allowing for a moderate dose-escalation that offers encouraging clinical results for biochemical control and survival in patients with prostate cancer after radical prostatectomy.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Hipofraccionamiento de la Dosis de Radiación , Anciano , Instituciones Oncológicas , Terapia Combinada , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Radioterapia Guiada por Imagen , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del Tratamiento
13.
Braz J Med Biol Res ; 53(2): e8901, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32049100

RESUMEN

The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.


Asunto(s)
Apoptosis , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sulfatasas/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adulto , Anciano , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Inmunohistoquímica , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ratones Desnudos , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-akt/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Sulfatasas/genética
14.
Clin Transl Oncol ; 22(9): 1499-1505, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31974820

RESUMEN

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.


Asunto(s)
Pancreatectomía/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Radiocirugia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
15.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;53(2): e8901, 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1055498

RESUMEN

The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.


Asunto(s)
Humanos , Animales , Femenino , Adulto , Persona de Mediana Edad , Anciano , Conejos , Sulfatasas/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Apoptosis , Sistema de Señalización de MAP Quinasas/fisiología , Sulfatasas/genética , Inmunohistoquímica , Células HeLa , Transducción de Señal , Estudios de Casos y Controles , Regulación Neoplásica de la Expresión Génica , Sistema de Señalización de MAP Quinasas/genética , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Ratones Desnudos , Estadificación de Neoplasias
16.
PLoS One ; 14(5): e0210453, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31063499

RESUMEN

Germination of seeds during the transportation or after prolonged storage naturally and inevitably decreases because of ageing, but germination potential can be partially restored with seed priming treatments. A novel attempt was made to investigate the effects of combined treatments and to optimize the conditions for naturally aged seeds of tall fescue (Festuca arundinacea Schreb.), orchardgrass (Dactylis glomerata L.) and Russian wild rye (Psathyrostachys juncea (Fisch.) Nevski) using an orthogonal activity level experimental design [factor A: Azospirillum brasilense concentration, factor B: three seed priming treatments (H2O, MgSO4 and H2O2) and factor C: different priming times]. Multivariate regression model analysis was applied to determine the interactive effects of pairwise factors (A and C) and to optimize experimental conditions. The results showed that the mixed treatments positively affected seed germination and seedling growth. The three seed priming treatments were the dominant factors for germination promotion, whereas the bacterial concentration had the largest effect on seedling growth and the activity of superoxide dismutase (SOD), especially root elongation. The malondialdehyde content was reduced, the activities of SOD, peroxidase and catalase were triggered, and ascorbate peroxidase activity was also affected by the co-treatment. The combined results of all determined attributes showed that A. brasilense bio-priming with H2O2 priming constituted the optimal combination. The optimal bacterial concentration of A. brasilense and the time of seed priming were 52.3 × 106 colony forming units (CFU) mL-1 and 17.0 h, respectively.


Asunto(s)
Azospirillum brasilense/fisiología , Germinación/fisiología , Poaceae/fisiología , Plantones/fisiología , Semillas/fisiología , Simbiosis , Biomarcadores
17.
J Stroke Cerebrovasc Dis ; 25(9): 2126-35, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27363623

RESUMEN

BACKGROUND: Many studies have investigated the association between the cyclooxygenase-2 (COX-2) gene polymorphism and ischemic stroke. However, results of these studies still remain controversial. To better explain the association between COX-2 polymorphisms (-765G/C and -1195G/A) and ischemic stroke risk, a meta-analysis was performed. METHODS: Relevant studies were identified from 4 Chinese databases (Chinese Biological Medical Literature database, Chinese National Knowledge Infrastructure database, Chongqing VIP database, and Chinese WANFANG database), PUBMED and EMBASE prior to December 2015. The strength of association between COX-2 polymorphism and ischemic stroke was evaluated by the odds ratio (OR) with 95% confidence interval (CI). Inconsistency index (I(2)) and the Cochran's Q statistic were used to check heterogeneity. Publication bias was evaluated by funnel plots and Egger's regression test. RESULTS: A total of 4086 ischemic stroke cases and 4747 controls were identified. Significant association between COX-2 -765G/C polymorphism and the risk of ischemic stroke was found in Brazilians and the African-Americans. The OR of (CC+GC versus GG) for the Brazilians and African-Americans were (6.328, 95% CI = 2.295-17.448) and (1.644, 95% CI = 1.060-2.551). In addition, the recessive model of the Brazilians gave an OR of 3.621 (95% CI: 1.519-8.630). Furthermore, the (GC versus GG) and the allele model of the African-Americans were (OR: 1.615, 95% CI = 1.015-2.572) and (OR: 1.422, 95% CI = 1.033-1.957). Significant association was also observed for COX-2 -1195G/A polymorphism in the subtypes of small vessel disease (SVD) of ischemic stroke. CONCLUSIONS: Our study suggests that COX-2 -765G/C and -1195G/A polymorphisms may contribute to susceptibility of ischemic stroke, specifically in Brazilians and the African-Americans, and those of SVD.


Asunto(s)
Isquemia Encefálica/complicaciones , Isquemia Encefálica/genética , Ciclooxigenasa 2/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genética , Negro o Afroamericano , Brasil , China , Estudios de Cohortes , Estudios Transversales , Análisis Mutacional de ADN , Bases de Datos Bibliográficas/estadística & datos numéricos , Femenino , Genotipo , Humanos , Masculino , Metaanálisis como Asunto
18.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;45(10): 921-928, Oct. 2012. ilus
Artículo en Inglés | LILACS | ID: lil-647744

RESUMEN

We investigated the contribution of the duration of overdistention (DOD) to rat bladder function and morphology and explored its possible molecular mechanisms. Bladder overdistention was induced in male Sprague-Dawley rats (200-250 g) by an infusion of saline. Forty rats were divided into 5 groups submitted to different DOD, i.e., 1, 2, 4, and 8 h, and control. Bladder function was evaluated by cystometry. Morphological changes were observed by light and transmission electron microscopy. Compared to control (44.567 ± 3.472 cmH2O), the maximum detrusor pressure of groups with 2-, 4- and 8-h DOD decreased significantly (means ± SEM): 32.774 ± 3.726, 31.321 ± 2.847, and 29.238 ± 3.724 cmH2O. With the increase of DOD, inflammatory infiltration and impairment of ultrastructure were more obvious in bladder tissue. Compared to control (1.90 ± 0.77), the apoptotic indexes of groups with 1-, 2-, 4-, and 8-h DOD increased significantly (6.47 ± 2.10, 10.66 ± 1.97, 13.91 ± 2.69, and 18.33 ± 3.28%). Compared to control (0.147 ± 0.031/0.234 ± 0.038 caspase 3/β-actin and Bax/Bcl-2 ratios), both caspase 3/β-actin and Bax/Bcl-2 ratios of 1-, 2-, 4-, and 8-h DOD increased significantly (0.292 ± 0.037/0.508 ± 0.174, 0.723 ± 0.173/1.745 ± 0.471, 1.104 ± 0.245/4.000 ± 1.048, and 1.345 ± 0.409/8.398 ± 3.332). DOD plays an important role in impairment of vesical function and structure. With DOD, pro-apoptotic factors increase and anti-apoptotic factors decrease, possibly contributing to the functional deterioration and morphological changes of the bladder.


Asunto(s)
Animales , Masculino , Ratas , Vejiga Urinaria/ultraestructura , Apoptosis , Modelos Animales de Enfermedad , Dilatación Patológica/patología , Dilatación Patológica/fisiopatología , Ratas Sprague-Dawley , Factores de Tiempo , Vejiga Urinaria/fisiopatología
19.
Braz J Med Biol Res ; 45(10): 921-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22735176

RESUMEN

We investigated the contribution of the duration of overdistention (DOD) to rat bladder function and morphology and explored its possible molecular mechanisms. Bladder overdistention was induced in male Sprague-Dawley rats (200-250 g) by an infusion of saline. Forty rats were divided into 5 groups submitted to different DOD, i.e., 1, 2, 4, and 8 h, and control. Bladder function was evaluated by cystometry. Morphological changes were observed by light and transmission electron microscopy. Compared to control (44.567 ± 3.472 cmH2O), the maximum detrusor pressure of groups with 2-, 4- and 8-h DOD decreased significantly (means ± SEM): 32.774 ± 3.726, 31.321 ± 2.847, and 29.238 ± 3.724 cmH2O. With the increase of DOD, inflammatory infiltration and impairment of ultrastructure were more obvious in bladder tissue. Compared to control (1.90 ± 0.77), the apoptotic indexes of groups with 1-, 2-, 4-, and 8-h DOD increased significantly (6.47 ± 2.10, 10.66 ± 1.97, 13.91 ± 2.69, and 18.33 ± 3.28%). Compared to control (0.147 ± 0.031/0.234 ± 0.038 caspase 3/ß-actin and Bax/Bcl-2 ratios), both caspase 3/ß-actin and Bax/Bcl-2 ratios of 1-, 2-, 4-, and 8-h DOD increased significantly (0.292 ± 0.037/0.508 ± 0.174, 0.723 ± 0.173/1.745 ± 0.471, 1.104 ± 0.245/4.000 ± 1.048, and 1.345 ± 0.409/8.398 ± 3.332). DOD plays an important role in impairment of vesical function and structure. With DOD, pro-apoptotic factors increase and anti-apoptotic factors decrease, possibly contributing to the functional deterioration and morphological changes of the bladder.


Asunto(s)
Vejiga Urinaria/ultraestructura , Animales , Apoptosis , Dilatación Patológica/patología , Dilatación Patológica/fisiopatología , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Vejiga Urinaria/fisiopatología
20.
J Toxicol Environ Health A ; 75(1): 36-49, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22047162

RESUMEN

Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)), with several As-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies suggested that indigenous Americans (AME) methylate As more efficiently; however, data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and As methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to As in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3-1053.5 µg/L, while percent AME (%AME) mean and range were 72.4 and 23-100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index [BMI], and TAs) multiple regression model showed that higher AME ancestry is significantly associated with lower percentage of urinary As excreted as MMA(V) (%uMMA) in this population (p < .01). Data also demonstrated a significant interaction between BMI and gender, indicating negative association between BMI and %uMMA, stronger in women than men (p < .01). Moreover, age and the AS3MT variants 7388 (intronic) and M287T (nonsynonymous) were also significantly associated with As methylation efficiency (p < .01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations.


Asunto(s)
Intoxicación por Arsénico/epidemiología , Arsénico/metabolismo , Arsénico/toxicidad , Contaminantes Químicos del Agua/toxicidad , Adulto , Factores de Edad , Anciano , Arsénico/orina , Intoxicación por Arsénico/complicaciones , Arsenicales/metabolismo , Arsenicales/orina , Índice de Masa Corporal , Femenino , Haplotipos , Humanos , Masculino , Metilación , Americanos Mexicanos , México/epidemiología , Persona de Mediana Edad , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/orina , Adulto Joven
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