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1.
Sci Rep ; 14(1): 7948, 2024 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575627

RESUMO

The aim of this study is to analyse the relationship between democratic quality and excess mortality produced in the year 2020 before COVID-19 vaccinations were generalised. Using cross-sectional data from 80 countries on five continents, multiple linear regression models between excess mortality, the general democracy index and its disaggregation into five categories: electoral process and pluralism, government functioning, political participation, political culture and civil liberties were estimated. The analysis also considered, public health spending per capita, overweight inhabitants, the average temperature of the country, population over 65 years of age, The KOF Globalisation Index, and the Gross National Income per capita as control variables. It was possible to establish a strong inverse association between excess mortality per million inhabitants and the general democracy index and four of its five categories. There was a particularly strong relationship between excess mortality and the political culture dimension (-326.50, p < 0.001). The results suggest that the higher the democratic quality of the political institutions of a State and particularly of their political culture the more improved the response and management of the pandemic was in preventing deaths and protecting their citizens more effectively. Conversely, countries with lower democracy index values have higher excess mortality. Quality democratic political institutions provide more effective public health policies in the face of the COVID-19 pandemic.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Democracia , Pandemias , Estudos Transversais , Política
2.
Front Plant Sci ; 15: 1323390, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38439988

RESUMO

The CRISPR/Cas9 ribonucleoprotein (RNP)-mediated technology represents a fascinating tool for modifying gene expression or mutagenesis as this system allows for obtaining transgene-free plants, avoiding exogenous DNA integration. Holm oak (Quercus ilex) has an important social, economic, and ecological role in the Mediterranean climate zones of Western Europe and North Africa and is severely affected by oak decline syndrome. Here we report the first example of the application of the CRISPR/Cas9-RNP technology in holm oak. Firstly, we evaluated the protoplast isolation from both in vitro leaves and proembryogenic masses. Proembryogenic masses represented the best material to get high protoplast yield (11 x 106 protoplasts/ml) and viability. Secondly, the protoplast transfection ability was evaluated through a vector expressing green fluorescence protein as marker gene of transfection, reaching a transfection percentage of 62% after 24 hours. CRISPR/Cas9 RNPs were successfully delivered into protoplasts resulting in 5.6% ± 0.5% editing efficiency at phytoene desaturase (pds) target genomic region. Protoplasts were then cultured in semisolid media and, after 45 days in culture, developed embryogenic calli were observed in a Murashige and Skoog media with half concentration of NH4NO3 and KNO3 supplemented with 0.1 mg/L benzylaminopurine and 0.1 mg/L 2,4-dichlorophenoxyacetic acid.

4.
Aliment Pharmacol Ther ; 59(7): 865-876, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38327102

RESUMO

BACKGROUND: There are few data on corticosteroids (CS)-sparing strategies for checkpoint inhibitor (ICI)-induced liver injury (ChILI). AIM: We aimed to assess the performance of a 2-step algorithm for severe ChILI, based on ICI temporary discontinuation (step-1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step-2). METHODS: Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening. RESULTS: From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti-PD1, 8(18.2%) anti-PD-L1, 3(6.8%) anti-CTLA-4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step-1) and 8/22 (36.4%) based on the degree of necroinflammation (step-2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non-improvement patients after ICI discontinuation. CD8+ HLA-DR expression (p = 0.028), central memory (p = 0.046) were lower in CS-free managed subjects, but effector-memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS-free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed. CONCLUSIONS: An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Humanos , Estudos Prospectivos , Corticosteroides/efeitos adversos , Imunoterapia/efeitos adversos , Biópsia , Transaminases
5.
Disabil Rehabil ; : 1-7, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38243921

RESUMO

PURPOSE.: Plantar fasciitis is the most frequent cause of heel pain. Custom-made plantar supports are a common treatment solution, while the application of kinesiology tape (KT) can be an effective measure to alleviate pain. The objective was to evaluate the effects of KT on the pain of patients with plantar fasciitis. METHODS.: Randomized controlled trial including participants with plantar fasciitis. There was an experimental group (n = 17), whose participants underwent a KT treatment, and a control (sham tape) group (n = 17). The pain, measured with a visual analog scale (VAS), was the primary outcome and was assessed daily until the fifth day of wearing the tape and 24 h after removing it. Inferential statistics looked for time, group, and time per group differences with CI at 95%. RESULTS.: The greatest between-group VAS difference was 3.5 points, and occurred at the 2-day follow-up assessment. Then, pain differences decreased over time until the last assessment point. Statistically significant time, group, and time*group differences were found with p < 0.001. CONCLUSION.: This study supports that KT is effective in reducing pain in the short term in patients with plantar fasciitis, and more effective than a sham intervention with tape.


Kinesiology tape (KT) reduces pain in patients with plantar fasciitis.Pain is reduced from the first day and the tape can be worn up to five days.KT is an effective solution prior to the application of orthopaedic treatment.

6.
Healthcare (Basel) ; 12(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38275550

RESUMO

Patients with multimorbidity have increased and more complex healthcare needs, posing their management a challenge for healthcare systems. This study aimed to describe their primary healthcare utilization and associated factors. A population-based cross-sectional study was conducted in a Spanish basic healthcare area including all patients with chronic conditions, differentiating between having multimorbidity or not. Sociodemographic, functional, clinical and service utilization variables were analyzed, stratifying the multimorbid population by the Adjusted Morbidity Groups (AMG) risk level, sex and age. A total of 6036 patients had multimorbidity, 64.2% being low risk, 28.5% medium risk and 7.3% high risk. Their mean age was 64.1 years and 63.5% were women, having on average 3.5 chronic diseases, and 25.3% were polymedicated. Their mean primary care contacts/year was 14.9 (7.8 with family doctors and 4.4 with nurses). Factors associated with primary care utilization were age (B-coefficient [BC] = 1.15;95% Confidence Interval [CI] = 0.30-2.01), female sex (BC = 1.04; CI = 0.30-1.78), having a caregiver (BC = 8.70; CI = 6.72-10.69), complexity (B-coefficient = 0.46; CI = 0.38-0.55), high-risk (B-coefficient = 2.29; CI = 1.26-3.32), numerous chronic diseases (B-coefficient = 1.20; CI = 0.37-2.04) and polypharmacy (B-coefficient = 5.05; CI = 4.00-6.10). This study provides valuable data on the application of AMG in multimorbid patients, revealing their healthcare utilization and the need for a patient-centered approach by primary care professionals. These results could guide in improving coordination among professionals, optimizing multimorbidity management and reducing costs derived from their extensive healthcare utilization.

7.
J Infect Public Health ; 17(3): 435-442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262081

RESUMO

BACKGROUND: There is little evidence regarding the characteristics of adults who self-reported not having had COVID-19 after two years of the pandemic. This study aimed to analyse the characteristics of no-COVID-19 respondents and the associated factors to better understand which may have conditioned not having had the disease as guidance to help in the design of better public health strategies. METHODS: This cross-sectional, observational study was conducted in the Spanish general population in a representative sample of 1051 adults who completed an online survey in September 2022. Multivariable logistic regression was performed to assess which factors were related to reporting not having had COVID-19. RESULTS: Almost half of the respondents (47.8%) reported not having ever had COVID-19. Significant differences were found between people who reported having had and not having had COVID-19 according to sex, age, education level, employment and living with children. No-COVID-19 respondents had greater concern and less fear of the disease and were more worried about the new variants. After the multivariable analysis, factors associated with no-COVID-19 respondents were male sex (OR)=1.40; 95% (CI=1.07-1.82), older age (OR=1.01; 95% CI=1.01-1.03), having a greater perception of disease severity if infected (OR=4.71; 95% CI=2.97-7.47), greater adherence to preventive measures (OR=1.02; 95% CI=1.01-1.03), and having received a complete vaccination schedule and booster dose (OR=1.56; 95% CI=1.03-2.36). CONCLUSIONS: Analysing the characteristics of people reporting not having had COVID-19 can support public health decision-makers in designing better interventions and facilitating the implementation of effective prevention and control measures to prepare for and respond to a possible future pandemic.


Assuntos
COVID-19 , Adulto , Criança , Humanos , Masculino , Feminino , Espanha/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Autorrelato
8.
J Exp Clin Cancer Res ; 43(1): 10, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38167224

RESUMO

BACKGROUND: The variability in responses to neoadjuvant treatment with anti-HER2 antibodies prompts to personalized clinical management and the development of innovative treatment strategies. Tumor-infiltrating Natural Killer (TI-NK) cells can predict the efficacy of HER2-targeted antibodies independently from clinicopathological factors in primary HER2-positive breast cancer patients. Understanding the mechanism/s underlying this association would contribute to optimizing patient stratification and provide the rationale for combinatorial approaches with immunotherapy. METHODS: We sought to uncover processes enriched in NK cell-infiltrated tumors as compared to NK cell-desert tumors by microarray analysis. Findings were validated in clinical trial-derived transcriptomic data. In vitro and in vivo preclinical models were used for mechanistic studies. Findings were analysed in clinical samples (tumor and serum) from breast cancer patients. RESULTS: NK cell-infiltrated tumors were enriched in CCL5/IFNG-CXCL9/10 transcripts. In multivariate logistic regression analysis, IFNG levels underlie the association between TI-NK cells and pathological complete response to neoadjuvant treatment with trastuzumab. Mechanistically, the production of IFN-É£ by CD16+ NK cells triggered the secretion of CXCL9/10 from cancer cells. This effect was associated to tumor growth control and the conversion of CD16 into CD16-CD103+ NK cells in humanized in vivo models. In human breast tumors, the CD16 and CD103 markers identified lineage-related NK cell subpopulations capable of producing CCL5 and IFN-É£, which correlated with tissue-resident CD8+ T cells. Finally, an early increase in serum CCL5/CXCL9 levels identified patients with NK cell-rich tumors showing good responses to anti-HER2 antibody-based neoadjuvant treatment. CONCLUSIONS: This study identifies specialized NK cell subsets as the source of IFN-É£ influencing the clinical efficacy of anti-HER2 antibodies. It also reveals the potential of serum CCL5/CXCL9 as biomarkers for identifying patients with NK cell-rich tumors and favorable responses to anti-HER2 antibody-based neoadjuvant treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Terapia Neoadjuvante , Linfócitos T CD8-Positivos , Receptor ErbB-2 , Trastuzumab/farmacologia , Células Matadoras Naturais , Resultado do Tratamento , Quimiocina CXCL9/uso terapêutico , Quimiocina CCL5
10.
Front Public Health ; 11: 1166317, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780448

RESUMO

Introduction: Identifying stakeholders' needs is crucial to informing decisions and policy development. This study aims to identify healthcare and social-related needs and effective strategies associated with COVID-19 from the first-person perspectives of patients and healthcare providers. Methods: Cross-sectional online survey design including qualitative open-ended questions, conducted in primary care and hospital settings across Spain, with 12 out of 19 regions represented. Adults aged 18 years and older, who (a) resided in Spain and had a history of COVID-19 or (b) worked as healthcare providers delivering direct or indirect care for people with COVID-19 in Spanish primary care or hospitals during 2020 were eligible to participate. Recruitment was conducted via social-media networks (Twitter, LinkedIn, and WhatsApp) and communication channels of key organizations including patient and professional associations and groups. A total of 182 people were invited to complete the surveys and 76 people completed the surveys (71% women), of which 33 were home-isolated patients, 14 were hospitalized patients, 16 were primary care professionals, and 13 were hospital care professionals. Results: A total of 327 needs and 86 effective strategies and positive aspects were identified across surveys and classified into the following overarching themes: (i) Accessibility, (ii) Basic needs, (iii) Clinical care, (iv) Person-and-family centered care, (v) Caring for the healthcare professional, (vi) Protocolization, information, health campaigns, and education, (vii) Resource availability, (viii) and Organizational needs/strategies. Discussion: Findings indicate the Spanish health and social care systems were generally unprepared to combat COVID-19. Implications for research, practice, and policy focus on integrating first-person perspectives as best practice to identify, prioritize and address needs to increase health and social care systems capacity and preparedness, as well as providing well-co-coordinated responses across government, healthcare, and non-government sectors to promote and protect the physical and mental health of all.


Assuntos
COVID-19 , Adulto , Humanos , Feminino , Masculino , Estudos Transversais , COVID-19/epidemiologia , COVID-19/terapia , Atenção à Saúde , Pessoal de Saúde/psicologia , Pacientes
11.
Artigo em Inglês | MEDLINE | ID: mdl-37769243

RESUMO

OBJECTIVES: Systemic sclerosis (SSc)-specific autoantibodies allow the diagnosis and predict the prognosis of SSc patients with different clinical characteristics. The aim of this study was to describe new SSc-related autoantibodies by a novel protein immunoprecipitation (IP) assay. METHODS: Serum samples and clinical data were collected from 307 SSc patients. Antinuclear autoantibodies were tested in all patients by indirect immunofluorescence (IIF) on HEp-2 cells. SSc-specific autoantibodies were evaluated with a commercial immunoblot and chemiluminescence immunoassay, and traditional RNA-IP. Patients negative for all these autoantibodies (n = 51) were further tested with a non-radioactive protein IP assay. Protein bands detected on SDS-PAGE were then analysed by mass spectrometry (MS) and confirmed by western blot (WB). Additional 56 patients with nucleolar pattern by IIF were tested by protein IP-WB. RESULTS: Five patients who underwent protein IP testing showed a 110-115kDa molecular weight band on SDS-PAGE and a homogeneous nucleolar pattern by IIF. MS identified the bands as nuclear valosin-containing protein-like (NVL). An additional positive patient was detected by IP-WB. As compared with the remaining 101 negative patients, anti-NVL positive patients showed a greater prevalence of calcinosis (100% vs 18.9%, p< 0.001), and cancer (66.7% vs 8.9%, p= 0.002), with a particular association with synchronous cancer (OR = 16.3; p= 0.024). CONCLUSION: We identified NVL as a new autoantibody target by a novel protein IP assay in SSc patients with a homogeneous nucleolar IIF pattern, testing negative for all known SSc-specific autoantibodies by commercial assays and RNA IP. Anti-NVL identifies a new clinical phenotype, characterized by calcinosis and cancer.

12.
Cancers (Basel) ; 15(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37760491

RESUMO

HER2-positive breast cancer accounts for 15-20% of all breast cancer cases. This subtype is characterized by an aggressive behavior and poor prognosis. Anti-HER2 therapies have considerably improved the natural course of the disease. Despite this, relapse still occurs in around 20% of patients due to primary or acquired treatment resistance, and metastasis remains an incurable disease. This article reviews the main mechanisms underlying resistance to anti-HER2 treatments, focusing on newer HER2-targeted therapies. The progress in anti-HER2 drugs includes the development of novel antibody-drug conjugates with improvements in the conjugation process and novel linkers and payloads. Moreover, trastuzumab deruxtecan has enhanced the efficacy of trastuzumab emtansine, and the new drug trastuzumab duocarmazine is currently undergoing clinical trials to assess its effect. The combination of anti-HER2 agents with other drugs is also being evaluated. The addition of immunotherapy checkpoint inhibitors shows some benefit in a subset of patients, indicating the need for useful biomarkers to properly stratify patients. Besides, CDK4/6 and tyrosine kinase inhibitors are also included in the design of new treatment strategies. Lapitinib, neratinib and tucatinib have been approved for HER2-positive metastasis patients, however clinical trials are currently ongoing to optimize combined strategies, to reduce toxicity, and to better define the useful setting. Clinical research should be strengthened along with the discovery and validation of new biomarkers, as well as a deeper understanding of drug resistance and action mechanisms.

13.
Clin. transl. oncol. (Print) ; 25(9): 2647-2664, sept. 2023. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-224131

RESUMO

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody–drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Genômica , Estadiamento de Neoplasias , Sociedades Médicas , Espanha
14.
BMJ Glob Health ; 8(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37380365

RESUMO

Visceral leishmaniasis is a vector-borne, protozoan disease with severe public health implications. Following the successful implementation of an elimination programme in South Asia, there is now a concerted endeavour to replicate these efforts in Eastern Africa based on the five essential elimination pillars of case management, integrated vector management, effective surveillance, social mobilisation and operational research. This article highlights how key social determinants (SD) of health (poverty, sociocultural factors and gender, housing and clustering, migration and the healthcare system) operate at five different levels (socioeconomic context and position, differential exposure, differential vulnerability, differential outcomes and differential consequences). These SD should be considered within the context of increasing the success of the five-pillar elimination programme and reducing inequity in health.


Assuntos
Leishmaniose Visceral , Humanos , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Determinantes Sociais da Saúde , África Oriental/epidemiologia , Ásia Meridional , Administração de Caso
15.
Clin Transl Oncol ; 25(9): 2647-2664, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37326826

RESUMO

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody-drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM.


Assuntos
Neoplasias da Mama , COVID-19 , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Pandemias , Consenso , Sistemas de Liberação de Medicamentos
16.
Diagnostics (Basel) ; 13(7)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37046475

RESUMO

Anti-nuclear (ANA) are present in approximately 90% of systemic sclerosis (SSc) patients and are key biomarkers in supporting the diagnosis and determining the prognosis of this disease. In addition to the classification criteria autoantibodies for SSc [i.e., anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA polymerase III], other autoantibodies have been associated with important SSc phenotypes. Among them, anti-U11/U12 ribonucleoprotein (RNP) antibodies, also known as anti-RNPC-3, were first reported in a patient with SSc, but very little is known about their association and clinical utility. The U11/U12 RNP macromolecular complex consists of several proteins involved in alternative mRNA splicing. More recent studies demonstrated associations of anti-anti-U11/U12 antibodies with SSc and severe pulmonary fibrosis as well as with moderate to severe gastrointestinal dysmotility. Lastly, anti-U11/U12 autoantibodies have been strongly associated with malignancy in SSc patients. Here, we aimed to summarize the knowledge of anti-U11/U12/RNPC-3 antibodies in SSc, including their seroclinical associations in a narrative literature review.

17.
Molecules ; 28(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37049769

RESUMO

Cheese is a product of animal origin with a high nutritional value, and it is one of the most consumed dairy foods in Mexico. In addition, Chihuahua cheese is the most consumed matured cheese in Mexico. In the production process of Chihuahua cheese, maturation is carried out by adding acid lactic microorganisms, mainly of the Lactococcus genus and, in some cases, also the Streptococcus and Lactobacillus genus. As part of the metabolism of fermenting microorganisms, biogenic amines can develop in matured foods, which result from the activity of amino decarboxylase enzymes. In cheeses, histamine and tyramine are the main amines that are formed, and the consumption of these represents a great risk to the health of consumers. In this work, the presence of biogenic amines (histamine and tyramine) was determined by HPLC at different times of the shelf life of Chihuahua cheeses. In addition, the presence of genes hdc and tdc that code for the enzymes responsible for the synthesis of these compounds (histidine and tyrosine decarboxylase, or HDC and TDC) was determined by molecular techniques. A significant correlation was observed between the presence of both histamine and tyramine at the end of shelf life with the presence of genes that code for the enzymes responsible for their synthesis.


Assuntos
Queijo , Histamina , Animais , Histamina/metabolismo , Tiramina , Aminas Biogênicas/análise , Lactobacillus/metabolismo
18.
Cancers (Basel) ; 15(7)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37046799

RESUMO

Trastuzumab treatment has significantly improved the prognosis of HER2-positive breast cancer patients. Despite this, resistance to therapy still remains the main clinical challenge. In order to evaluate the implication of microRNAs in the trastuzumab response, we performed a microRNA array in parental and acquired trastuzumab-resistant HER2-positive breast cancer cell lines. Our results identified miR-146a-5p as the main dysregulated microRNA. Interestingly, high miR-146a-5p expression in primary tumor tissue significantly correlated with shorter disease-free survival in HER2-positive breast cancer patients. The gain- and loss-of-function of miR-146a-5p modulated the response to trastuzumab. Furthermore, the overexpression of miR-146a-5p increased migration and angiogenesis, and promoted cell cycle progression by reducing CDKN1A expression. Exosomes from trastuzumab-resistant cells showed a high level of miR-146a-5p expression compared with the parental cells. In addition, the co-culture with resistant cells' exosomes was able to decrease in sensitivity and increase the migration capacities in trastuzumab-sensitive cells, as well as angiogenesis in HUVEC-2 cells. Collectively, these data support the role of miR-146a-5p in resistance to trastuzumab, and demonstrate that it can be transferred by exosomes conferring resistance properties to other cells.

19.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36835014

RESUMO

Due to the lack of specific targets, cytotoxic chemotherapy still represents the common standard treatment for triple-negative breast patients. Despite the harmful effect of chemotherapy on tumor cells, there is evidence that treatment could modulate the tumor microenvironment in a way favoring the propagation of the tumor. In addition, the lymphangiogenesis process and its factors could be involved in this counter-therapeutic event. In our study, we have evaluated the expression of the main lymphangiogenic receptor VEGFR3 in two triple-negative breast cancer in vitro models, resistant or not to doxorubicin treatment. The expression of the receptor, at mRNA and protein levels, was higher in doxorubicin-resistant cells than in parental cells. In addition, we confirmed the upregulation of VEGFR3 levels after a short treatment with doxorubicin. Furthermore, VEGFR3 silencing reduced cell proliferation and migration capacities in both cell lines. Interestingly, high VEGFR3 expression was significantly positively correlated with worse survival in patients treated with chemotherapy. Furthermore, we have found that patients with high expression of VEGFR3 present shorter relapse-free survival than patients with low levels of the receptor. In conclusion, elevated VEGFR3 levels correlate with poor survival in patients and with reduced doxorubicin treatment efficacy in vitro. Our results suggest that the levels of this receptor could be a potential marker of meager doxorubicin response. Consequently, our results suggest that the combination of chemotherapy and VEGFR3 blockage could be a potentially useful therapeutic strategy for the treatment of triple-negative breast cancer.


Assuntos
Doxorrubicina , Neoplasias de Mama Triplo Negativas , Receptor 3 de Fatores de Crescimento do Endotélio Vascular , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Recidiva Local de Neoplasia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
20.
J Cosmet Dermatol ; 22(3): 916-920, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36374629

RESUMO

OBJECTIVE: Onychocryptosis is one of the most prevalent onychopathies, being a frequent reason for consultation in podiatric clinical practice. Conservative treatments are the first therapeutic choice, with nail remodeling using clotrimazole gel emerging as an alternative, although its medium-term effectiveness is unknown. The objective of this study was therefore to compare the efficacy of the technique of nail retraining using gauze bandaging with that of nail remodeling for the conservative treatment of stage I and IIA onychocryptosis. METHODS: An analytical, randomized clinical trial study was performed following a longitudinal and prospective design. A sample was selected of 20 subjects presenting stage I and IIA onychocryptosis. Of these, 10 cases formed the group of nail retraining using gauze bandaging, and the other 10 the nail remodeling group. The presence of recurrence in a 3-month period was evaluated. RESULTS: Before the intervention, the patients in the retraining group presented pain of 6.7 ± 1.9 vs. 6.8 ± 1.6 in the remodeling group, with no significant difference between the two (p = 0.900). After the 3-month follow-up period, seven of the retraining group patients presented recurrence of onychocryptosis vs. only one in the remodeling group. CONCLUSION: The technique of nail remodeling has a lower recurrence rate than that of nail retraining with gauze bandaging, with the pain, inflammation, and infection reported being less, and with greater patient satisfaction.


Assuntos
Unhas Encravadas , Humanos , Unhas Encravadas/terapia , Tratamento Conservador , Unhas , Dor , Bandagens
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