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BACKGROUND: Angiogenesis is a process that many tumors depend on for growth, development, and metastasis. Vascular endothelial growth factor (VEGF) is one of the major players in tumor angiogenesis in several tumor types, including melanoma. VEGF inhibition is achieved by bevacizumab, a humanized monoclonal antibody that binds with high affinity to VEGF and prevents its function. In order to successfully enable in vivo VEGF expression imaging in a murine melanoma model, we previously labeled bevacizumab with [99mTc]Tc. We observed that this was feasible, but it had prolonged blood circulation and delayed tumor uptake. OBJECTIVE: The aim of this study was to develop a radiolabeled Fab bevacizumab fragment, [99mTc]Tc-HYNICFab( bevacizumab), for non-invasive in vivo VEGF expression molecular imaging. METHODS: Flow cytometry was used to examine VEGF presence in the murine melanoma cell line (B16-F10). Bevacizumab was digested with papain for six hours at 37°C to produce Fab(bevacizumab), which was then conjugated to NHS-HYNIC-Tfa for radiolabeling with [99mTc]Tc. Stability and binding affinity assays were also evaluated. Biodistribution and single photon emission computed tomography/computed tomography (SPECT/CT) were performed at 1, 3, and 6 h (n = 4) after injection of [99mTc]Tc-HYNIC-Fab(Bevacizumab) in normal and B16-F10 tumor-bearing C57Bl/6J mice. RESULTS: Using flow cytometry, it was shown that the B16-F10 murine melanoma cell line has intracellular VEGF expression. Papain incubation resulted in the complete digestion of bevacizumab with good purity and homogeneity. The radiolabeling yield of [99mTc]Tc-HYNIC-Fab(bevacizumab) was 85.00 ± 6.06%, with a specific activity of 291.87 ± 18.84 MBq/mg (n=3), showing in vitro stability. Binding assays demonstrated significant intracellular in vitro VEGF expression. Fast blood clearance and high kidney and tumor uptake were observed in biodistribution and SPECT/CT studies. CONCLUSIONS: We present the development and evaluation of [99mTc]Tc-HYNIC-Fab(bevacizumab), a novel molecular VEGF expression imaging agent that may be used for precision medicine in melanoma and potentially in other VEGF-expressing tumors.
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Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.
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Anticorpos Monoclonais , Radioisótopos do Iodo , Losartan , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Losartan/farmacologia , Losartan/farmacocinética , Losartan/administração & dosagem , Distribuição Tecidual , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/farmacocinética , Tecnécio , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Linhagem Celular Tumoral , Feminino , Proteína Tumoral 1 Controlada por TraduçãoRESUMO
In 2018, Complex Post Traumatic Stress Disorder (CPTSD) was officially recognized as a distinct syndrome in the International Classification of Diseases, 11th Revision (ICD-11). This recognition aimed to differentiate between neurotic disorders secondary to stressful situations and somatoform disorders, and disorders specifically associated with stress. The inclusion of CPTSD in the ICD-11 marked the culmination of two decades of research focused on understanding its symptoms, treatments, and risk factors. However, despite the progress made, a comprehensive meta-analysis to elucidate the specific risk factors and impact on the development of CPTSD is still lacking. The objective of this article is to conduct such a meta-analysis. A total of 24 studies were selected for analysis, and the findings revealed several key risk factors associated with the development of CPTSD. The main risk factor identified is having experienced sexual abuse in childhood (k = 12; OR = 2.880). In addition, childhood physical abuse (k = 11; OR = 2.841), experiencing emotional neglect during childhood (k = 5; OR = 2.510), physical abuse throughout life (k = 8; OR = 2.149) and being a woman (k = 13; OR = 1.726) were also significant risk factors.
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Delitos Sexuais , Transtornos de Estresse Pós-Traumáticos , Feminino , Humanos , Classificação Internacional de Doenças , Fatores de Risco , Delitos Sexuais/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , MasculinoRESUMO
INTRODUCCIÓN: El estudio presenta perfiles integrales para usuarios de los Centros de Salud primaria de la comuna de Alto Hospicio. OBJETIVO: Conocer los perfiles de usuarios inscritos en los Centros de Salud de la comuna de Alto Hospicio desde una perspectiva integral e incorporando indicadores de satisfacción y conocimiento acerca del Modelo de Atención Integral de Salud Familiar y Comunitaria (MAIS). MATERIAL Y MÉTODO: Se elaboró un instrumento conformado por ocho dimensiones y 73 ítems, el cual se aplicó en cuatro centros de Atención de Salud Primaria de la comuna. Se realizó un muestreo aleatorio simple por cada Centro. En total se encuestaron a 1.124 personas, se obtuvo una representatividad de entre 95% y 93% de confianza, con niveles de significación que van de 5% a 7%. RESULTADOS: La caracterización usuaria pone en relevancia la diversidad de perfiles atendidos en cada Centro de Salud y revela problemáticas generales como la escasa información recibida respecto del modelo de atención familiar, el desconocimiento de los servicios prestados por los Centros de Salud y la dificultad de enfrentar situaciones de salud mental en el contexto de la pandemia COVID-19. CONCLUSIONES: Aquellos Centros de Salud que transmiten mayor información del MAIS presentan mejores indicadores respecto al conocimiento de los servicios de salud y de satisfacción usuaria. En el marco de la implementación del Modelo de Salud Familiar, es relevante conocer los perfiles de usuarios según las características de cada Centro de Salud, su población y territorio, y compartir buenas prácticas entre los Centros.
BACKGROUND: The study presents comprehensive profiles of Primary Health Care Centers of the Alto Hospicio Commune users. OBJECTIVE: To characterize users registered in the Health Centers of Alto Hospicio Commune from a comprehensive perspective, including satisfaction indicators and knowledge about the Comprehensive Family and Community Health Care Model (MAIS). METHODS: A questionnaire of 8 dimensions and 73 items was designed and applied in 4 Primary Health Care Centers in the commune. Four simple random samplings were applied. In total, 1,124 users were surveyed. The confidence and significance levels were between 95%-93% and 5%-7%, respectively. RESULTS: The user profile highlights the diversity in each Health Care Center and reveals general problems such as the lack of information regarding the family care model and services provided by the Health Care Centers and the difficulty of facing mental health situations in the context of the COVID-19 pandemic. CONCLUSIONS: Those Health Centers that provide more information about MAIS show better indicators regarding knowledge of health services and user satisfaction. The changes in public health policies and the implementation of the Comprehensive Family and Community Health Care Model require clarifying user profiles according to the characteristics of each health center, its population, and the territory, as well as sharing best practices between health centers.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Atenção Primária à Saúde/estatística & dados numéricos , Serviços de Saúde Comunitária/organização & administração , Serviços de Saúde Comunitária/estatística & dados numéricos , COVID-19/epidemiologia , Chile , Saúde da Família , Estudos Transversais , Inquéritos e Questionários , Prestação Integrada de Cuidados de Saúde/organização & administração , SARS-CoV-2RESUMO
BACKGROUND: The study presents comprehensive profiles of Primary Health Care Centers of the Alto Hospicio Commune users. OBJECTIVE: To characterize users registered in the Health Centers of Alto Hospicio Commune from a comprehensive perspective, including satisfaction indicators and knowledge about the Comprehensive Family and Community Health Care Model (MAIS). METHODS: A questionnaire of 8 dimensions and 73 items was designed and applied in 4 Primary Health Care Centers in the commune. Four simple random samplings were applied. In total, 1,124 users were surveyed. The confidence and significance levels were between 95%-93% and 5%-7%, respectively. RESULTS: The user profile highlights the diversity in each Health Care Center and reveals general problems such as the lack of information regarding the family care model and services provided by the Health Care Centers and the difficulty of facing mental health situations in the context of the COVID-19 pandemic. CONCLUSIONS: Those Health Centers that provide more information about MAIS show better indicators regarding knowledge of health services and user satisfaction. The changes in public health policies and the implementation of the Comprehensive Family and Community Health Care Model require clarifying user profiles according to the characteristics of each health center, its population, and the territory, as well as sharing best practices between health centers.
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COVID-19 , Serviços de Saúde Comunitária , Atenção Primária à Saúde , Chile , Humanos , Atenção Primária à Saúde/estatística & dados numéricos , COVID-19/epidemiologia , Masculino , Feminino , Serviços de Saúde Comunitária/organização & administração , Serviços de Saúde Comunitária/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Pessoa de Meia-Idade , Prestação Integrada de Cuidados de Saúde/organização & administração , Adulto Jovem , SARS-CoV-2 , Adolescente , Saúde da Família , Idoso , Estudos TransversaisRESUMO
Background: Borderline personality disorder (BPD) is characterized by symptoms associated with difficulties in emotion regulation, altered self-image, impulsivity, and instability in personal relationships. A relationship has been found between BPD symptoms and altered neuropsychological processes. Studies of event-related potentials (ERP) measured with electroencephalogram (EEG) have found neural correlates related to BPD symptoms. Of note is the P300 component, considered a potential mental health biomarker for trauma-associated disorders. However, no meta-analysis has been found to demonstrate this relationship.Objectives: To evaluate the relationship between the P300 component and BPD symptoms. To evaluate the relationship of other ERP components with BPD symptoms.Methods: The method and procedure were adjusted to the PRISMA checklist. The search was performed in three databases: WOS, Scopus and PubMed. A Random Effects Model was used to perform the analysis of the studies. In addition, a meta-regression was performed with % women, Gini and GDP. Finally, a descriptive analysis of the main results found between P300, other ERP components (LPP, P100 and ERN/Ne) and BPD symptoms was performed.Results: From a review of 485 articles, a meta-analysis was performed with six articles that met the inclusion criteria. A moderate, positive relationship was found between the P300 component and BPD symptoms (REM = .489; p < .001). It was not possible to perform meta-analyses for other ERP components (LPP, P100 and ERN/Ne) due to the low number of articles found.Conclusion: The idea that P300 could be considered for use as a biomarker to identify altered neural correlates in BPD is reinforced. In addition, a moderating effect of inequality (Gini) was detected.
The P300 component of event-related potentials could be considered for use as a possible biomarker to identify altered neural correlates in Borderline Personality Disorder.There is support for the proposition that an altered P300 would be present in disorders related to exposure to traumatic events.P300 could be used to evaluate the therapeutic processes associated with the clinical symptoms of Borderline Personality Disorder.
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Transtorno da Personalidade Borderline , Humanos , Feminino , Masculino , Transtorno da Personalidade Borderline/diagnóstico , Potenciais Evocados/fisiologia , Eletroencefalografia , Comportamento Impulsivo , BiomarcadoresRESUMO
Abstract In recent years, nanocarriers have been studied as promising pharmaceutical tools for controlled drug-delivery, treatment-efficacy follow-up and disease imaging. Among them, X-shaped amphiphilic polymeric micelles (Tetronic®, poloxamines) display great potential due to their biocompatibility and non-toxic effects, among others. In the present work, polymeric micelles based on the T1307 copolymer were initially decorated with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-fluorophore in order to determinate its in vivo biodistribution on 4T1 tumor-bearing mice. However, unfavorable results with this probe led to two different strategies. On the one hand, the BODIPY-micelle-loaded, L-T1307-BODIPY, and on the other hand, the 99mTc-micelle-radiolabeled, L-T1307- 99m Tc, were analyzed separately in vivo. The results indicated that T1307 accumulates mainly in the stomach, the kidneys, the lungs and the tumor, reaching the maximum organ-accumulation 2 hours after intravenous injection. Additionally, and according to the results obtained for L-T1307- 99m Tc, the capture of the polymeric micelles in organs could be observed up to 24 hours after injection. The results obtained in this work were promising towards the development of new radiotracer agents for breast cancer based on X-shaped polymeric micelles.
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Animais , Feminino , Camundongos , Eficácia , Diagnóstico , Injeções Intravenosas/classificação , Micelas , Neoplasias/diagnóstico , Estômago/anormalidades , Preparações Farmacêuticas/análise , Estratégias de Saúde , Pulmão/anormalidadesRESUMO
BACKGROUND: Ending December 2019, the world had to face to COVID-19. Latin America and the Caribbean suffered the effects where the contiguous and the number of deaths has been significant. Studies indicate that older adults with some degree of cognitive impairment are at greater risk of worsening their cognitive status and mental health, for this reason it's exposed that social isolation and loneliness has harmful effects on the health of this population. This mini-review inquires on the effects of COVID-19 due to social isolation on neuropsychiatric symptoms (NPS) in Latin American older adults with and without dementia. METHOD: A search was carried out in PubMed, SCOPUS, and ScienceDirect identifying all articles published up to July 31, 2021 using the keywords "social isolation", "lockdown", "quarantine", "COVID-19",, "neuropsychiatric symptoms ", "neurobehavioral", "dementia"," mild cognitive impairment "," Older People ", "aging", "elderly". Two independent reviewers screened and selected appropriate articles and a third researcher helped resolve disagreements. The selected articles met the following criteria: written in English, Spanish or Portuguese, original article; focused on elderly subjects, articles that provided information on the NPS effects in Latin American populations during the COVID-19 pandemic. The review was based on the PRISMA Statement and used the SIGN criteria. RESULT: From 61 articles recovered from electronic databases (PubMed, Science Direct and Scopus) 10 of them were chosen for this review. The majority of the articles reported in a general way a negative impact on the mental health of the population in Latin America. They referred to a significant increase in the anxiety and depression symptoms. The majority of the articles were studies developed in Brazil, Argentina and Chile. CONCLUSION: The COVID-19 has shown a negative impact on the mental health of older adults. Latin America is a region with important socio-sanitary problems which increase the impact of the pandemic in SNP, especially in older adults. It's necessary to increase the studies in Latin America that glimpse the real situation in the region.
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Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external image acquisitions and evaluation of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, for the first time, in a metastatic melanoma model as molecular imaging probe for in vivo diagnostic, as well as in a non-metastatic melanoma model. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. In addition, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 h after probes injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.
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Aptâmeros de Nucleotídeos , Moléculas de Adesão Celular , Melanoma/diagnóstico por imagem , Imagem Molecular/métodos , Receptores Proteína Tirosina Quinases , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Corantes Fluorescentes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , RadioquímicaRESUMO
Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on 99mTc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with 99mTc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of 99mTc-HYNIC liposome and 99mTc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that 99mTc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.
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Melanoma Experimental/metabolismo , Niacinamida/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/farmacocinética , Animais , Linhagem Celular Tumoral , Lipossomos , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/administração & dosagem , Niacinamida/química , Permeabilidade/efeitos dos fármacos , Cintilografia/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Tecnécio/administração & dosagem , Tecnécio/química , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. OBJECTIVE: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. METHODS: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. RESULTS: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with 99mTc via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. CONCLUSION: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.
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Anticorpos Monoclonais Humanizados/química , Carbocianinas/química , Imagem Molecular , Mieloma Múltiplo/diagnóstico por imagem , Compostos de Organotecnécio/química , Compostos Radiofarmacêuticos/química , Humanos , Receptores de Interleucina-6/análiseRESUMO
Aptamers are oligonucleotides that have the characteristic of recognizing a target with high affinity and specificity. Based on our previous studies, the aptamer probe Sgc8-c-Alexa647 is a promising tool for molecular imaging of PTK7, which is an interesting biomarker in cancer. In order to improve the delivery of this probe as well as create a novel drug delivery nanosystem targeted to the PTK7 receptor, we evaluate the co-association between the probe and preformed nanostructures. In this work, preformed pegylated liposomes (PPL) and linear and branched pristine polymeric micelles (PMs), based on PEO-PPO-PEO triblock copolymers were used: poloxamer F127® and poloxamines T1307® and T908®. For it, Sgc8-c-Alexa647 and its co-association with the different nanostructures was exhaustively analyzed. DLS analysis showed nanometric sizes, and TEM and AFM showed notable differences between free- and co-associated probe. Likewise, all nanosystems were evaluated on A20 lymphoma cell line overexpressing PTK7, and the confocal microscopy images showed distinctness in cellular uptake. Finally, the biodistribution in BALB/c mice bearing lymphoma-tumor and pharmacokinetic study revealed an encouraging profile for T908-probe. All data obtained from this work suggested that PMs and, more specifically T908 ones, are good candidates to improve the pharmacokinetics and the tumor uptake of aptamer-based probes.
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2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to 14 times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (greater than 75%), monodisperse nanometric particle sizes (PDI = 0.180-0.335), adequate Z-potentials (-1.59 to -26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).
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Background: Aptamers represent an emerging class of oligonucleotides that have the ability to bind ligands with high affinity. Sgc8-c aptamer recognizes PTK7, a member of the catalytically defective receptor protein tyrosine kinase family that is upregulated in various cancers, including hemato-oncological malignancies. Herein, an Sgc8-c-NOTA-radiolabeled probe was prepared for theranostic purpose. Materials and Methods: In this work, an Sgc8-c-radiolabeled probe against PTK7 was prepared, and biological evaluations-pharmacokinetic studies, biodistribution analysis, and in vivo molecular imaging-were performed. To obtain the radiolabeled probe, a modified 5'-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator NOTA, and subsequently labeled with 67Ga with high yield and radiochemical purity. The precursor, Sgc8-c-NOTA, the radio probe Sgc8-c-NOTA-67Ga, and its nonradioactive complex, Sgc8-c-NOTA-69/71Ga, were purified by reverse-phase high-performance liquid chromatography and characterized by electrospray ionization mass spectrometry. The binding ability of Sgc8-c-NOTA-67Ga was studied in vitro against purified PTK7 receptor. In addition, the binding was also evidenced against the hemato-oncological A20 cell line, derived from B lymphocytes, and the corresponding A20-green fluorescent protein (GFP)-transfected cells. The proof of concept was performed on A20-GFP tumor-bearing mice, in which the biodistribution of the radiolabeled probe was evaluated through imaging, using X-ray, fluorescence, and γ modalities. The specific uptake of the probe was confirmed by blocking with the Sgc8-c aptamer in an in vivo competition assay. Results: The biodistribution results showed considerable uptake in tumor since 2 h, with highest at 48 h postinjection. However, the blood and muscle ID/g (injected dose per gram of tissue) activities were decreasing with time and tumor/no-target ratios increasing to 20 at 24 h postinjection. These results are consistent with the in vivo images. Conclusions: This study supports the utility of Sgc8-c-NOTA radiolabeled as a theranostic agent.
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Aptâmeros de Nucleotídeos/uso terapêutico , Neoplasias Hematológicas/terapia , Radioquímica/métodos , Animais , Feminino , Humanos , CamundongosRESUMO
La probabilidad de nuevos eventos cardiovasculares mayores (ECVM) en pacientes luego de un infarto agudo del miocardio depende de diferentes variables, como el tiempo que haya pasado después del primer evento, el escenario de presentación (síndrome coronario agudo con/sin elevación del ST) y los factores de riesgo asociados. Dichos eventos se han relacionado con la respuesta proinï¬amatoria persistente1, la actividad plaquetaria y la actividad de la trombina2. La llegada de medicamentos con actividad antitrombótica más potente y especíï¬ca en puntos clave del proceso trombótico ha permitido evaluar su efecto en el escenario de la prevención secundaria antitrombótica intensiva luego del primer año de un infarto del miocardio3. En este tipo de prevención se han propuesto diferentes estrategias terapéuticas, entre ellas se ha extendiendo la doble terapia antiplaquetaria (DTA) (4, iniciando terapias antiplaquetarias adicionales5, o usando dosis bajas de anticoagulantes directos más aspirina6. Sin embargo, las características similares y, a su vez, heterogéneas en esta población, generan dudas de cuándo, en quiénes y cómo usar este tipo de terapia.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Infarto do Miocárdio , Preparações Farmacêuticas , Síndrome Coronariana Aguda , Prevenção SecundáriaRESUMO
Background: Carboranylanilinoquinazoline-hybrids, developed for boron neutron capture therapy, have demonstrated cytotoxicity against murine-glioma cells with EGFR-inhibition ability. In addition, their adequate aqueous/metabolic stabilities and ability to cross blood-brain barrier make them good leads as to become antiglioma drugs. Aim: Analyze drug-like properties of representative carboranylanilinoquinazolines. Materials & methods: To expand carboranylanilinoquinazolines therapeutic spectrum, we studied their ability to act against glioma-mammal cells, U-87 MG and other tyrosine kinase-overexpress cells, HT-29. Additionally, we predicted theoretically and studied experimentally drug-like properties, in other words, organization for economic cooperation and development-recommended toxicity-studies and, due to some aqueous-solubility problems, and vehicularization for oral and intravenous administrations. Conclusion: We have identified a promising drug-candidate with broad activity spectrum, appropriate drug-like properties, adequate toxicological behavior and able ability to be loaded in suitable vehicles.
Assuntos
Compostos de Anilina/química , Antineoplásicos/química , Neoplasias Encefálicas/radioterapia , Receptores ErbB/antagonistas & inibidores , Glioma/radioterapia , Inibidores de Proteínas Quinases/química , Quinazolinas/química , Compostos de Anilina/farmacologia , Animais , Antineoplásicos/farmacologia , Barreira Hematoencefálica/metabolismo , Terapia por Captura de Nêutron de Boro/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Colesterol/química , Composição de Medicamentos/métodos , Desenvolvimento de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Fosfatidilcolinas/química , Poliaminas/química , Polietilenos/química , Polipropilenos/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/metabolismo , Quinazolinas/farmacologia , Solubilidade , ÁguaRESUMO
The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community-based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct-acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0-18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4-96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7-98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI -0.24-0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.
Assuntos
Competência Clínica , Hepatite C/epidemiologia , Assistência ao Paciente , Padrões de Prática Médica , Telemedicina , Adulto , Idoso , Antivirais/uso terapêutico , Argentina/epidemiologia , Quimioterapia Combinada , Feminino , Geografia , Hepatite C/diagnóstico , Hepatite C/terapia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Resposta Viral Sustentada , Telemedicina/métodosRESUMO
El granuloma gigantocelular representa un tumor no odontogénico que se localiza por dentro del endostio de los maxilares (central) o en el periostio (periférico). Corresponde al 3-5 % de todas las lesiones benignas de los maxilares. Es más frecuente en niños y adultos jóvenes. Se presenta como un tumor de crecimiento lento y asintomático. Preferentemente, se ubica en la mandíbula, en la región de los incisivos, caninos y premolares. Se informa sobre un paciente de 6 años de edad que, conjuntamente con la extracción del premolar temporario inferior, presentó un tejido granulomatoso de crecimiento lento en la región premolar izquierda. La toma de la biopsia fue demostrativa para granuloma gigantocelular. Se realizó el tratamiento quirúrgico, con buena evolución, sin evidencia de recidiva hasta la actualidad. Es importante el diagnóstico temprano de esta lesión por el alto poder destructivo local que presenta y la derivación oportuna para el tratamiento quirúrgico.
Giant cell granuloma represents a non-odontogenic tumor. It is located inside the endosteum of the jaws (central) or in the periosteum (peripheral). Although it is a benign disease process, it can also be locally destructive. This condition is a slow-growing, asymptomatic lesion that usually affects children and young adults, predominantly females in its peripheral presentation and males in its central presentation. The mandible, the region of the incisors, canines and premolars are more affected. The etiology of the giant cell granuloma still remains to be defined. It has been reported that the origin of this lesion could be triggered by trauma or inflammation and hormonal factors. A 6-year-old patient presents a slow-growing lesion in the tooth extraction's region, two months ago. The treatment is surgical. It is important to have an early diagnosis because of the high local destructive behavior and timely referral because the treatment is surgical.