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1.
Mycopathologia ; 189(1): 10, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38231407

RESUMEN

BACKGROUND: Mucormycosis and aspergillosis are angioinvasive infections mainly occurring in immunocompromised patients. However, mixed infection with mucormycosis and aspergillosis in post-COVID-19 patients is rare. In this report, we will report four cases and comprehensively review the published literature on COVID-19 associated mixed infection of aspergillosis and mucormycosis. METHOD: Besides four of our cases, we searched for published articles using PubMed/MEDLINE, Scopus, and Web of Science databases from the beginning of 2020 until October 2023. RESULT: During the COVID-19 pandemic, we analyzed 52 cases (4 from our research and 48 from other studies). The most common underlying disease (59.6%) was diabetes mellitus. However, 19.2% of COVID-19 patients had no underlying condition. Interestingly, rhino-orbital-cerebral mucormycosis featured prominently in India and Iran, while other countries primarily reported a higher prevalence of pulmonary cases. CONCLUSION: In conclusion, this study highlights the presence of mixed aspergillosis and mucormycosis in COVID-19 patients who previously had common underlying diseases or even a healthy immune system. Therefore, managing COVID-19 patients should involve screening serum and respiratory samples using biomarkers to detect superinfections.


Asunto(s)
Aspergilosis , COVID-19 , Coinfección , Mucormicosis , Humanos , Mucormicosis/complicaciones , Mucormicosis/diagnóstico , Mucormicosis/epidemiología , Pandemias , COVID-19/complicaciones
2.
Ophthalmic Plast Reconstr Surg ; 39(6S): S29-S39, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38054983

RESUMEN

PURPOSE: Graves orbitopathy (GO) is the most common extrathyroidal manifestation of Graves disease. Although its pathogenesis is not fully elucidated, GO is commonly considered an autoimmune disease due to loss of self-tolerance against autoantigens shared by thyroid epithelial cells and orbital fibroblasts. High-dose intravenous glucocorticoids (ivGCs) are the most used treatment for moderate-to-severe, active GO, but the addition of other immunomodulating treatments can improve the efficacy of ivGCs. Among the various risk factors that can affect the occurrence of GO, cholesterol may be worthy of interest. Since 2015 the role of cholesterol and cholesterol-lowering medications has been investigated. The purpose of this review is to discuss this topic, thereby offering new therapeutic opportunities for patients with GO. METHODS: We searched PubMed for studies published between January 1, 1980 and June 1, 2023, using the search terms "Graves orbitopathy," "thyroid eye disease," "Graves ophthalmopathy," "thyroid ophthalmopathy," "thyroid-associated ophthalmopathy," "endocrine ophthalmopathy," "cholesterol," "lipids," "statins," "low-density lipoprotein," "atorvastatin," and "cholesterol-lowering drugs." Only English-language articles were included. RESULTS: A correlation between low-density lipoprotein cholesterol and the risk of GO development has been reported. Furthermore, low-density lipoprotein cholesterol has been proposed as a risk factor that can affect the course of GO and the response to ivGCs. The protective role of cholesterol-lowering medications in preventing GO has been also investigated. Statin treatment was found to have potential benefits in reducing the risk of GO in patients with Graves disease. Given these findings, measurement of low-density lipoprotein cholesterol and treatment of hypercholesterolemia in patients with moderate-to-severe, active GO may be considered before starting ivGCs administration. Recently, a randomized clinical trial aimed at investigating the effects of statins in GO suggested that the addition of oral atorvastatin to ivGCs improves the overall outcome of moderate-to-severe, active GO in hypercholesterolemic patients given ivGCs. CONCLUSIONS: Overall, statins seem to have a preventive and therapeutic role in moderate-to-severe active GO. Their efficacy can be related to cholesterol-lowering activity, pleiotropic actions, and interaction with methylprednisolone.


Asunto(s)
Enfermedad de Graves , Oftalmopatía de Graves , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Atorvastatina , Glucocorticoides/uso terapéutico , Lipoproteínas LDL , Colesterol , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Ophthalmic Plast Reconstr Surg ; 39(6S): S65-S80, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38054987

RESUMEN

PURPOSE: Dysthyroid optic neuropathy (DON) is a sight-threatening complication of thyroid eye disease (TED). This review provides an overview of the epidemiology, pathogenesis, diagnosis, and current therapeutic options for DON. METHODS: A literature review. RESULTS: DON occurs in about 5% to 8% of TED patients. Compression of the optic nerve at the apex is the most widely accepted pathogenic mechanism. Excessive stretching of the nerve might play a role in a minority of cases. Increasing age, male gender, smoking, and diabetes mellitus have been identified as risk factors. Diagnosis of DON is based on a combination of ≥2 clinical findings, including decreased visual acuity, decreased color vision, relative afferent pupillary defect, visual field defects, or optic disc edema. Orbital imaging supports the diagnosis by confirming apical crowding or optic nerve stretching. DON should be promptly treated with high-dose intravenous glucocorticoids. Decompression surgery should be performed, but the response is incomplete. Radiotherapy might play a role in the prevention of DON development and may delay or avoid the need for surgery. The advent of new biologic-targeted agents provides an exciting new array of therapeutic options, though more research is needed to clarify the role of these medications in the management of DON. CONCLUSIONS: Even with appropriate management, DON can result in irreversible loss of visual function. Prompt diagnosis and management are pivotal and require a multidisciplinary approach. Methylprednisolone infusions still represent first-line therapy, and surgical decompression is performed in cases of treatment failure. Biologics may play a role in the future.


Asunto(s)
Oftalmopatía de Graves , Papiledema , Humanos , Masculino , Glucocorticoides/uso terapéutico , Oftalmopatía de Graves/complicaciones , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/terapia , Metilprednisolona , Nervio Óptico
4.
Ophthalmic Plast Reconstr Surg ; 39(6S): S19-S28, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38054982

RESUMEN

PURPOSE: Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. Patients may be severely affected with eyelid retraction, exophthalmos, diplopia, pain, and threatened vision. Autoantibodies against thyroid-stimulating hormone receptor and insulin-like growth factor 1 receptor have shown associations with pathophysiological and clinical traits. Autoantibodies against thyroid-stimulating hormone receptor is in current clinical use as biomarker, but not with unambiguous diagnostic performance. A biomarker with high diagnostic accuracy and/or prognostic capability would be of immense value in diagnosing TED, especially in subclinical cases or when TED precedes the thyroid dysfunction. This article is a literature review on molecular biomarkers of TED. METHODS: A literature search was performed using PubMed and Embase. Studies on molecular biomarkers in blood, tear fluid, and urine were included in the review. RESULTS: Forty-six papers were included, of which 30, 14, and 2 studies on biomarkers in blood, tears, and urine, respectively. Fourteen of the papers evaluated the diagnostic performance of various biomarkers, 12 in blood and 2 in tears. Most studies evaluated single biomarkers, but 3 tested a panel of several markers. Except for autoantibodies against thyroid-stimulating hormone receptor, the reported diagnostic performances for the biomarkers were not confirmed in independent cohorts. In 32 studies, no or insufficient performance data were given, but the findings indicated involvement of various biologic mechanisms in TED including inflammation, oxidative stress, fibrosis, lipid metabolism, and ocular surface microflora. CONCLUSIONS: Currently, serum autoantibodies against thyroid-stimulating hormone receptor is the only molecular biomarker with clinical utility in patients with TED. Several potential biomarkers have been investigated, and particularly panels of multiple biomarkers in tears are promising. To improve patient care, biomarkers in TED should be studied further.


Asunto(s)
Enfermedad de Graves , Oftalmopatía de Graves , Humanos , Oftalmopatía de Graves/diagnóstico , Biomarcadores , Autoanticuerpos , Tirotropina
5.
Mycopathologia ; 188(5): 783-792, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37672164

RESUMEN

BACKGROUND: Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs. OBJECTIVES: To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran. PATIENTS/METHODS: A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol. RESULT: A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9 years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31 days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5 µg/ml) demonstrated the highest potency against Mucorales. CONCLUSION: Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.


Asunto(s)
COVID-19 , Diabetes Mellitus , Mucorales , Mucormicosis , Masculino , Humanos , Persona de Mediana Edad , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Mucormicosis/epidemiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Centros de Atención Terciaria , Irán/epidemiología , Estudios Prospectivos , Diabetes Mellitus/tratamiento farmacológico
6.
Int J Mol Sci ; 24(14)2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37511113

RESUMEN

Many biological and physiological events, including growth, development, and metabolism of reproductive and non-reproductive tissues in men and women, are regulated by estrogens and estrogen receptors (ERs) [...].


Asunto(s)
Estrógenos , Receptores de Estrógenos , Masculino , Femenino , Humanos , Receptores de Estrógenos/metabolismo , Estrógenos/metabolismo , Reproducción
7.
Int J Mol Sci ; 24(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37047814

RESUMEN

Breast cancer is the most common cancer and the deadliest among women worldwide. Estrogen signaling is closely associated with hormone-dependent breast cancer (estrogen and progesterone receptor positive), which accounts for two-thirds of tumors. Hormone therapy using antiestrogens is the gold standard, but resistance to these treatments invariably occurs through various biological mechanisms, such as changes in estrogen receptor activity, mutations in the ESR1 gene, aberrant activation of the PI3K pathway or cell cycle dysregulations. All these factors have led to the development of new therapies, such as selective estrogen receptor degraders (SERDs), or combination therapies with cyclin-dependent kinases (CDK) 4/6 or PI3K inhibitors. Therefore, understanding the estrogen pathway is essential for the treatment and new drug development of hormone-dependent cancers. This mini-review summarizes current literature on the signalization, mechanisms of action and clinical implications of estrogen receptors in breast cancer.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/genética , Antagonistas de Estrógenos/uso terapéutico , Estrógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Estrógenos/metabolismo , Transducción de Señal
8.
J Appl Toxicol ; 42(7): 1121-1136, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34964157

RESUMEN

In comparison with analytical tools, bioassays provide higher sensitivity and more complex evaluation of environmental samples and are indispensable tools for monitoring increasing in anthropogenic pollution. Nevertheless, the disadvantage in cellular assays stems from the material variability used within the assays, and an interlaboratory adaptation does not usually lead to satisfactory test sensitivities. The aim of this study was to evaluate the influence of material variability on CXCL12 secretion by T47D cells, the outcome of the CXCL-test (estrogenic activity assay). For this purpose, the cell line sources, sera suppliers, experimental and seeding media, and the amount of cell/well were tested. The multivariable linear model (MLM), employed as an innovative approach in this field for parameter evaluation, identified that all the tested parameters had significant effects. Knowledge of the contributions of each parameter has permitted step-by-step optimization. The most beneficial approach was seeding 20,000 cells/well directly in treatment medium and using DMEM for the treatment. Great differences in both basal and maximal cytokine secretions among the three tested cell lines and different impacts of each serum were also observed. Altogether, both these biologically based and highly variable inputs were additionally assessed by MLM and a subsequent two-step evaluation, which revealed a lower variability and satisfactory reproducibility of the test. This analysis showed that not only parameter and procedure optimization but also the evaluation methodology must be considered from the perspective of interlaboratory method adaptation. This overall methodology could be applied to all bioanalytical methods for fast multiparameter and accurate analysis.


Asunto(s)
Estrógenos , Contaminantes Químicos del Agua , Bioensayo , Línea Celular , Monitoreo del Ambiente/métodos , Estrógenos/toxicidad , Estrona , Modelos Lineales , Reproducibilidad de los Resultados
9.
Orbit ; 41(4): 437-446, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34030586

RESUMEN

PURPOSE: Idiopathic sclerosing orbital inflammatory syndrome (ISOIS) is a rare, progressive and hard to control disease. There is a deep gap of evidence regarding application of disease-modifying drugs (DMD) regimen as a potentially effective treatment for orbital inflammatory diseases. We aimed to report the results of using DMDs and discuss the concept of applying this modality of treatment in patients with ISOIS. METHODS: This was a prospective interventional case series conducted in a tertiary university-based hospital. Biopsy proven patients with active ISOIS were included. Systematic criteria were developed to define and measure disease activity and monitor response to treatment. A DMD regimen including an anti-tumor necrosis factor alpha (anti-TNF alpha) agent plus azathioprine and low-dose corticosteroids were used. Comprehensive ophthalmic, orbital and systemic assessments were performed during each visit. RESULTS: Five eligible patients with primary ISOIS were included. Mean age was 34.20 (SD = 13.33, range 19-53) years. Three had unilateral and two had bilateral involvement. Four had diffuse orbital involvement pattern and progressive worsening of visual functions, reduced extraocular motility and proptosis. In one patient the disease was localized to extraocular muscle and lacrimal gland. Disease activity was decreased and stabilized after DMDs regimen in all patients. Mean follow up was 32.80 (SD = 30.80, range: 12-86) months. CONCLUSION: Biologic DMD (b-DMD) including anti-TNF alpha, corticosteroid and azathioprine were effective in decreasing disease activity and could change course of the disease. This study supports the concept of using b-DMD regimen in treatment of ISOIS.


Asunto(s)
Azatioprina , Seudotumor Orbitario , Adulto , Azatioprina/uso terapéutico , Humanos , Persona de Mediana Edad , Seudotumor Orbitario/diagnóstico por imagen , Seudotumor Orbitario/tratamiento farmacológico , Estudios Prospectivos , Inhibidores del Factor de Necrosis Tumoral , Adulto Joven
10.
Microb Pathog ; 158: 105018, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34098021

RESUMEN

This study aimed to determine the prevalence, the causative agents, clinical features, and the risk factors associated with the fungal rhinosinusitis in a tertiary health center with a view to providing valid grounds that may guide healthcare professionals to effectively prevent, control, and treat fungal infections. All patients were subjected to diagnostic nasal endoscopy and CT scan of paranasal sinuses and FRS were confirmed by routine and complementary mycological and molecular methods. The inclusion criteria for invasive FRS were: confirmed diagnosis of IFRS according to the guidelines of the EORTC/MSG criteria (i.e., clinical, microbiological, and histological evidence of invasive fungal infection). From a total of 512 suspected patients, FRS was confirmed in 108 cases (21.1%). Our results showed FB (38/108; 35.2%) is the most common form of FRS followed by AIFRS (33/108; 30.6%), AFS (32/108; 29.6%), and CIFRS (5/108; 4.6%). A. flavus and Rhizopus oryzae were the most common causes of infection in AFS, FB, CIFRS, and AIFRS, respectively. Univariate analysis of variables predictive of AIFRS revealed 3 variables significantly associated with AIFRS. These included mucosal abnormalities of the middle turbinate and septum, and specifically, necrosis of the middle turbinate (P < .0001). Microbiological cultures, although useful for mycological speciation, are less sensitive. Furthermore, we used molecular methods to confirm the identity of some isolates that were not detectable using routine methods. Our data showed that the molecular methods and histologic diagnosis in all patients were more sensitive than the unenhanced sinus CT scan, and conventional microbiological methods.


Asunto(s)
Micosis , Sinusitis , Hongos/genética , Humanos , Micosis/diagnóstico por imagen , Micosis/epidemiología , Nariz , Sinusitis/diagnóstico por imagen , Tomografía Computarizada por Rayos X
11.
Mycoses ; 64(10): 1238-1252, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34096653

RESUMEN

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.


Asunto(s)
Antifúngicos/uso terapéutico , COVID-19/complicaciones , Coinfección , Mucormicosis/tratamiento farmacológico , Mucormicosis/mortalidad , Síndrome de Dificultad Respiratoria/mortalidad , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , COVID-19/patología , Caspofungina/uso terapéutico , Comorbilidad , Estudios Transversales , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/mortalidad , Diabetes Mellitus/patología , Quimioterapia Combinada , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Mucormicosis/patología , Síndrome de Dificultad Respiratoria/microbiología , Síndrome de Dificultad Respiratoria/patología , Triazoles/uso terapéutico , Adulto Joven , Tratamiento Farmacológico de COVID-19
12.
Ophthalmic Plast Reconstr Surg ; 37(3S): S11-S18, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32618822

RESUMEN

PURPOSE: The International Council of Ophthalmology (ICO) is currently developing a series of standardized, internationally validated, teaching tool for key ophthalmic surgical procedures called the Ophthalmology Surgical Competency Assessment Rubrics (OSCARs). This study aims to develop an OSCAR for external dacryocystorhinostomy (ExDCR). METHODS: An international panel of content experts, representing Argentina, India, U.A.E., United Kingdom, and the U.S.A. was established and worked to develop the rubric using a range of online collaboration tools. The team used the standardized OSCAR template as a baseline, developing explicit behavioral descriptors (the behavior and performance expected for each step) that were reviewed and modified with successive models. Learners were scored on a modified 4-point Dreyfus scale of skill acquisition (novice, beginner, advanced beginner, competent) with the removal of the expert domain. The tool was then reviewed by a secondary panel of international content experts, representing Brazil, India, Iran, Singapore, United Kingdom, and the U.S.A. RESULTS: The final OSCAR ExDCR tool was developed in alignment with the ICO-OSCAR standard. Nineteen agreed and weighted stems were produced. Specific comments with regards to the parameters and wording were incorporated to formulate the final rubric, which was internationally agreed and demonstrated face and content validity. CONCLUSIONS: The OSCAR ExDCR is skill and behavior based, has ICO agreed standards for assessment, and provides learners with specific targets for improvement. Although the OSCAR tool has face and content validity, further development could better elucidate its precise role.


Asunto(s)
Dacriocistorrinostomía , Internado y Residencia , Oftalmología , Competencia Clínica , Educación de Postgrado en Medicina , Evaluación Educacional , Humanos , India , Oftalmología/educación , Singapur , Reino Unido
13.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33451133

RESUMEN

Breast cancer (BC) is the most common cancer among women worldwide. More than 70% of BC cases express estrogen receptor alpha (ERα), a central transcription factor that stimulates the proliferation of breast cancer cells, usually in the presence of estrogen. While most cases of ER-positive BC initially respond to antiestrogen therapies, a high percentage of cases develop resistance to treatment over time. The recent discovery of mutated forms of ERα that result in constitutively active forms of the receptor in the metastatic-resistance stage of BC has provided a strong rationale for the development of new antiestrogens. These molecules targeting clinically relevant ERα mutants and a combination with other pharmacological inhibitors of specific pathways may constitute alternative treatments to improve clinical practice in the fight against metastatic-resistant ER-positive BC. In this review, we summarize the latest advances regarding the particular involvement of point mutations of ERα in endocrine resistance. We also discuss the involvement of synonymous ERα mutations with respect to co-translational folding of the receptor and ribosome biogenesis in breast carcinogenesis.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/etiología , Neoplasias de la Mama/metabolismo , Mutación , Receptores de Estrógenos/genética , Animales , Antineoplásicos Hormonales/farmacología , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Antagonistas de Estrógenos/farmacología , Antagonistas de Estrógenos/uso terapéutico , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor alfa de Estrógeno/química , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Estrógenos/farmacología , Estrógenos/uso terapéutico , Femenino , Humanos , Terapia Molecular Dirigida , Mutación Missense , Receptores de Estrógenos/antagonistas & inhibidores , Receptores de Estrógenos/química , Receptores de Estrógenos/metabolismo , Mutación Silenciosa , Relación Estructura-Actividad
14.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33466512

RESUMEN

Approximately 80% of breast cancer (BC) cases express the estrogen receptor (ER), and 30-40% of these cases acquire resistance to endocrine therapies over time. Hyperactivation of Akt is one of the mechanisms by which endocrine resistance is acquired. Apigenin (Api), a flavone found in several plant foods, has shown beneficial effects in cancer and chronic diseases. Here, we studied the therapeutic potential of Api in the treatment of ER-positive, endocrine therapy-resistant BC. To achieve this objective, we stably overexpressed the constitutively active form of the Akt protein in MCF-7 cells (named the MCF-7/Akt clone). The proliferation of MCF-7/Akt cells is partially independent of estradiol (E2) and exhibits an incomplete response to the anti-estrogen agent 4-hydroxytamoxifen, demonstrating the resistance of these cells to hormone therapy. Api exerts an antiproliferative effect on the MCF-7/Akt clone. Api inhibits the proliferative effect of E2 by inducing G2/M phase cell cycle arrest and apoptosis. Importantly, Api inhibits the Akt/FOXM1 signaling pathway by decreasing the expression of FOXM1, a key transcription factor involved in the cell cycle. Api also alters the expression of genes regulated by FOXM1, including cell cycle-related genes, particularly in the MCF-7/Akt clone. Together, our results strengthen the therapeutic potential of Api for the treatment of endocrine-resistant BC.


Asunto(s)
Apigenina/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Proteína Forkhead Box M1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Línea Celular Tumoral , Células Endocrinas/efectos de los fármacos , Células Endocrinas/metabolismo , Estrógenos/metabolismo , Femenino , Humanos , Células MCF-7 , Transducción de Señal/efectos de los fármacos
15.
Int J Mol Sci ; 21(4)2020 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-32085612

RESUMEN

Recent studies strongly support the use of the aryl hydrocarbon receptor (AhR) as a therapeutic target in breast cancer. Glyceollins, a group of soybean phytoalexins, are known to exert therapeutic effects in chronic human diseases and also in cancer. To investigate the interaction between glyceollin I (GI), glyceollin II (GII) and AhR, a computational docking analysis, luciferase assays, immunofluorescence and transcriptome analyses were performed with different cancer cell lines. The docking experiments predicted that GI and GII can enter into the AhR binding pocket, but their interactions with the amino acids of the binding site differ, in part, from those interacting with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Both GI and GII were able to weakly and partially activate AhR, with GII being more potent. The results from the transcriptome assays showed that approximately 10% of the genes regulated by TCDD were also modified by both GI and GII, which could have either antagonistic or synergistic effects upon TCDD activation. In addition, we report here, on the basis of phenotype, that GI and GII inhibit the migration of triple-negative (ER-, PgR-, HER2NEU-) MDA-MB-231 breast cancer cells, and that they inhibit the expression of genes which code for important regulators of cell migration and invasion in cancer tissues. In conclusion, GI and GII are AhR ligands that should be further investigated to determine their usefulness in cancer treatments.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Pterocarpanos/farmacología , Receptores de Hidrocarburo de Aril/metabolismo , Sitios de Unión , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Pterocarpanos/química , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Receptores de Estrógenos/metabolismo , Transducción de Señal/efectos de los fármacos , Transcriptoma/genética
16.
Graefes Arch Clin Exp Ophthalmol ; 256(1): 209-218, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28986670

RESUMEN

PURPOSE: Intravenously administered erythropoietin (EPO) was firstly commenced (phase 1) in patients with indirect traumatic optic neuropathy (TON) by this group in 2011. It was re-tested by another group (phase 2) in 2014. This multicenter clinical trial was designed to compare its effect with intravenous steroid and observation. METHODS: Included were TON patients ≥5 years of age and with trauma-treatment interval of ≤3 weeks. Follow-up visits were set at 1, 2, 3, 7, 14, 30, and at least 90 days after treatment. EPO and methylprednisolone were infused intravenously every day for three consecutive days. Primary outcome measure was change in the best corrected visual acuity (BCVA). Secondary outcomes included change in color vision and relative afferent pupillary defect (RAPD), side effects, and factors affecting the final visual improvement. RESULTS: Out of 120 patients, 100 (EPO: 69, steroid: 15, observation: 16) were finally included. All three groups showed a significant improvement of BCVA which was not significantly different between the groups (adjusted for pretreatment BCVA). Color vision was significantly improved in the EPO group. Late treatment (>3 days) (odds ratio = 2.53) and initial BCVA of NLP (odds ratio = 5.74) significantly worsened visual recovery. No side effect was observed in any group. CONCLUSION: EPO, steroid, and observation showed a significant improvement of BCVA in patients with TON. Initial BCVA of NLP and late treatment (>3 days) were significant risk factors for visual improvement.


Asunto(s)
Eritropoyetina/administración & dosificación , Metilprednisolona/administración & dosificación , Enfermedades del Nervio Óptico/tratamiento farmacológico , Traumatismos del Nervio Óptico/complicaciones , Agudeza Visual , Adolescente , Adulto , Anciano , Niño , Preescolar , Visión de Colores , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiología , Traumatismos del Nervio Óptico/diagnóstico , Resultado del Tratamiento , Adulto Joven
17.
J Neuroophthalmol ; 38(2): 167-171, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29300238

RESUMEN

BACKGROUND: Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. METHODS: In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA. RESULTS: Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90-0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90-0.00 logMAR). VA significantly increased in the last follow-up examination (P < 0.0001). Age and time to EPO treatment after methanol ingestion were not significantly related to final VA. No ocular or systemic complications occurred in our patient cohort. CONCLUSIONS: Intravenous EPO appears to improve VA in patients with methanol optic neuropathy and may represent a promising treatment for this disorder.


Asunto(s)
Eritropoyetina/uso terapéutico , Metanol/toxicidad , Enfermedades del Nervio Óptico/tratamiento farmacológico , Solventes/toxicidad , Adolescente , Adulto , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Oftalmoscopía , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnóstico , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Tomografía de Coherencia Óptica , Agudeza Visual/efectos de los fármacos , Adulto Joven
18.
Ophthalmic Plast Reconstr Surg ; 34(2): e41-e43, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29049099

RESUMEN

The authors aim to report a 68-year-old patient presenting with acute swelling and redness of orbital area diagnosed initially as orbital cellulitis. Surgical excision was decided based on clinical and imaging findings with the diagnosis of pleomorphic adenoma of the lacrimal gland. Lacrimal gland pleomorphic adenoma usually presents with painless gradual swelling of upper eyelid. In an exceptionally rare circumstance, this case showed acute orbital inflammation, and imaging findings of orbital inflammation mostly focused around the cystic space of the lacrimal gland tumor. Histologic evaluation confirmed a ruptured cystic space of pleomorphic adenoma with foreign body-type inflammatory reaction. The authors propose spontaneous rupture of cystic space in the lacrimal gland pleomorphic adenoma as underlying mechanism for acute presentation of this tumor. Imaging and clinical characteristics and also prognostic implication of this phenomenon are discussed.


Asunto(s)
Adenoma Pleomórfico/patología , Neoplasias del Ojo/patología , Enfermedades del Aparato Lagrimal/patología , Celulitis Orbitaria/patología , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Rotura Espontánea
19.
Int J Mol Sci ; 19(4)2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29614754

RESUMEN

Comprehension of compound interactions in mixtures is of increasing interest to scientists, especially from a perspective of mixture risk assessment. However, most of conducted studies have been dedicated to the effects on gonads, while only few of them were. interested in the effects on the central nervous system which is a known target for estrogenic compounds. In the present study, the effects of estradiol (E2), a natural estrogen, and genistein (GEN), a phyto-estrogen, on the brain ER-regulated cyp19a1b gene in radial glial cells were investigated alone and in mixtures. For that, zebrafish-specific in vitro and in vivo bioassays were used. In U251-MG transactivation assays, E2 and GEN produced antagonistic effects at low mixture concentrations. In the cyp19a1b-GFP transgenic zebrafish, this antagonism was observed at all ratios and all concentrations of mixtures, confirming the in vitro effects. In the present study, we confirm (i) that our in vitro and in vivo biological models are valuable complementary tools to assess the estrogenic potency of chemicals both alone and in mixtures; (ii) the usefulness of the ray design approach combined with the concentration-addition modeling to highlight interactions between mixture components.


Asunto(s)
Aromatasa/metabolismo , Encéfalo/metabolismo , Estradiol/farmacología , Genisteína/farmacología , Animales , Animales Modificados Genéticamente , Aromatasa/genética , Encéfalo/efectos de los fármacos , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
20.
Orbit ; 37(6): 401-404, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29442541

RESUMEN

PURPOSE: The International Council of Ophthalmology (ICO) is currently developing a series of standardized, internationally validated, teaching tools for key ophthalmic surgical procedures called the Ophthalmology Surgical Competency Assessment Rubrics (OSCARs). This study aims to develop an OSCAR for anterior approach ptosis surgery. METHODS: An international panel of content experts, representing Australia, India, Iran, Italy, Turkey, UK, and the USA was established and worked to develop the rubric using a range of online collaboration tools. The team used the standardised OSCAR template as a baseline, developing explicit behavioural descriptors (the behaviour and performance expected for each step) that were reviewed and modified with successive models. Learners were scored a modified 4-point Dreyfus scale of skill acquisition (novice, beginner, advanced beginner, competent) with the removal of the expert domain. RESULTS: The final OSCAR ptosis tool was developed in alignment with the ICO-OSCAR standard. Seventeen agreed and weighted stems were produced. Domains such as communication and postoperative complications were removed from this rubric as they are evaluated in other spheres of residency training. Specific comments with regard to the parameters and wording were incorporated to formulate the final rubric, which was internationally agreed and demonstrated face and content validity. CONCLUSIONS: The OSCAR for anterior approach ptosis is skill and behaviour-based, has ICO agreed standards for assessment and provides learners with specific targets for improvement. Although the OSCAR ptosis tool has face and content validity, further development could better elucidate its precise role.


Asunto(s)
Blefaroptosis/cirugía , Competencia Clínica/normas , Educación de Postgrado en Medicina/normas , Procedimientos Quirúrgicos Oftalmológicos/normas , Oftalmología/educación , Evaluación Educacional , Humanos , Internacionalidad
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