RESUMEN
PURPOSE: To assess the effect of the Coronavirus disease 2019 (COVID-19) pandemic on cataract surgery by residents who had mandatory surgical simulator training during residency. METHODS: In this retrospective, observational analytical study, the total number of cataract surgeries and surgical complications by all senior residents of 2019 (2019 class; prepandemic) and 2020 (2020 class; affected by the reduced number of elective surgeries due to the COVID-19 pandemic) were collected and compared. All residents had routine mandatory cataract surgery training on a virtual surgical simulator during residency. The total score obtained by these residents on cataract challenges of the surgical simulator was also evaluated. RESULTS: The 2020 and 2019 classes performed 1275 and 2561 cataract surgeries, respectively. This revealed a reduction of 50.2% in the total number of procedures performed by the 2020 class because of the pandemic. The incidence of surgical complications was not statistically different between the two groups (4.2% in the 2019 class and 4.9% in the 2020 class; p=0.314). Both groups also did not differ in their mean scores on the simulator's cataract challenges (p<0.696). CONCLUSION: Despite the reduction of 50.2% in the total number of cataract surgeries performed by senior residents of 2020 during the COVID-19 pandemic, the incidence of surgical complications did not increase. This suggests that surgical simulator training during residency mitigated the negative effects of the reduced surgical volume during the pandemic.
Asunto(s)
COVID-19 , Catarata , Internado y Residencia , Humanos , Pandemias/prevención & control , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/prevención & control , Competencia ClínicaRESUMEN
ABSTRACT Purpose: To assess the effect of the coronavirus disease 2019 (COVID-19) pandemic on cataract surgery by residents who had mandatory surgical simulator training during residency. Methods: In this retrospective, observational analytical study, the total number of cataract surgeries and surgical complications by all senior residents of 2019 (2019 class; prepandemic) and 2020 (2020 class; affected by the reduced number of elective surgeries due to the COVID-19 pandemic) were collected and compared. All residents had routine mandatory cataract surgery training on a virtual surgical simulator during residency. The total score obtained by these residents on cataract challenges of the surgical simulator was also evaluated. Results: The 2020 and 2019 classes performed 1275 and 2561 cataract surgeries, respectively. This revealed a reduction of 50.2% in the total number of procedures performed by the 2020 class because of the pandemic. The incidence of surgical complications was not statistically different between the two groups (4.2% in the 2019 class and 4.9% in the 2020 class; p=0.314). Both groups also did not differ in their mean scores on the simulator's cataract challenges (p<0.696). Conclusion: Despite the reduction of 50.2% in the total number of cataract surgeries performed by senior residents of 2020 during the COVID-19 pandemic, the incidence of surgical complications did not increase. This suggests that surgical simulator training during residency mitigated the negative effects of the reduced surgical volume during the pandemic.
RESUMEN
Drug delivery systems of natural antimicrobial compounds, such as copaiba oil (CO), have become relevant in the scientific community due to the recent prevalence of the public health complications related to antibiotic resistance. Electrospun devices act as an efficient drug delivery system for these bioactive compounds, reducing systemic side effects and increasing the effectiveness of the treatment. In this way, the present study aimed to evaluate the synergistic and antimicrobial effect of the direct incorporation of different concentrations of CO in a poly(L-co-D,L lactic acid) and natural rubber (NR) electrospun membrane. It was observed that CO showed bacteriostatic and antibacterial effects against S. aureus in antibiogram assays. The prevention of biofilm formation was confirmed via scanning electron microscopy. The test with crystal violet demonstrated strong bacteria inhibition in membranes with 75% CO. A decrease in hydrophilicity, observed in the swelling test, presented that the addition of CO promotes a safe environment for the recovery of injured tissue while acting as an antimicrobial agent. In this way, the study showed strong bacteriostatic effects of the CO incorporation in combination with electrospun membranes, a suitable feature desired in wound dressings in order to promote a physical barrier with prophylactic antimicrobial properties to avoid infections during tissue healing.
RESUMEN
Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. Objectives: The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant. Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. Results: One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. Conclusion: A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations. Significance statement: A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.
RESUMEN
PURPOSE: To assess anterior, posterior, and total corneal astigmatism in a large sample of Brazilian patients. METHODS: In this retrospective cross-sectional study, all patients whose corneas were imaged with the Galilei G6 (Ziemer Ophthalmology) between January 2017 and February 2019 at HOPE Eye Hospital, in Recife, Brazil, were eligible to participate. Anterior, posterior, and total corneal astigmatism values were collected and analyzed. RESULTS: The study included 3,253 eyes of 1,919 patients. The mean magnitude of the anterior, posterior, and total corneal astigmatism was 1.50 ± 1.11, 0.34 ± 0.15, and 1.29 ± 0.98 diopters (D), respectively. Corneal astigmatism was greater than 0.50 D in the anterior cornea of 86.3% of eyes (2,807 eyes) and in the posterior cornea of 13.2% of eyes (429 eyes). Vertical alignment of the steepest corneal meridian was observed in the anterior cornea of 74.5% of eyes (2,423 eyes) and in the posterior cornea of 93.1% of eyes (3,029 eyes). The correlation between the astigmatism magnitude of the anterior and posterior cornea was strong when the steep anterior meridian was aligned vertically (r = 0.720; P < .001), and absent when it was aligned horizontally (r = 0.102; P = .036). CONCLUSIONS: Corneal astigmatism values in the Brazilian population were similar to those found in other ethnicities, suggesting that toric calculators, nomograms, coefficients of adjustment, and formulas that were developed based on astigmatism values of other populations may be used in Brazilian patients with comparable accuracy. [J Refract Surg. 2023;39(1):56-60.].
Asunto(s)
Astigmatismo , Enfermedades de la Córnea , Humanos , Astigmatismo/diagnóstico , Brasil/epidemiología , Topografía de la Córnea , Estudios Retrospectivos , Estudios Transversales , CórneaRESUMEN
Background. Chemokine and chemokine-receptor polymorphisms have been associated with protection against HIV infection and delayed progression to AIDS, whereas polymorphisms in IFNλ4 (formerly IL28B) have been associated with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) development. Evolutionary selection against ancestral genes differs among human populations, resulting in varying risks of acquiring and developing viral diseases. Methods. DNA samples from 434 patients infected with HIV-1 and/or co-infected with HTLV-1/-2, and samples from 74 HIV and HTLV non-infected individuals from São Paulo, Brazil, were divided into five groups: HIV-naïve, n=160; HIV-ART, n=180; HIV/HTLV-1, n=53; HIV/HTLV-2, n=41; and control, n=74. These samples were analyzed for CCR5-∆32deletion, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 single nucleotide polymorphisms using PCR and PCR-RFLP techniques. These polymorphisms' genotype and allele frequencies were calculated and compared among groups using logistic regression analysis. Results. All polymorphism profiles described in the literature were detected in this study. The wild-type genotype predominated in all genes analyzed except for IFNλ4 rs12979860. Statistical differences in allele frequencies among groups were detected in the CCR5 and CCR2 genes, with a high frequency of ∆32 in HIV-naïve vs. HIV-ART (OR 2.45, P=0.037) and a minus mutant allele A (CCR2-64I) in HIV-naïve vs. HIV/HTLV-1 (OR 1.90, P=0.048), HIV-ART vs. HIV/HTLV-1 (OR 2.62, P=0.003), and HIV/ART vs. HIV/HTLV-2 (OR 2.42, P=0.016). Conclusions. The polymorphism profiles detected in the study groups corroborate the profiles described in racial admixed populations. High CCR2-64I mutant allele frequencies were detected in HIV/HTLV-1/-2 co-infected individuals, and CCR5-∆32 showed predictive value for ART initiation. (AU)
Asunto(s)
Polimorfismo Genético , Brasil , Virus Linfotrópico T Tipo 1 Humano , Virus Linfotrópico T Tipo 2 Humano , VIH-1 , Quimiocinas , Receptores de QuimiocinaRESUMEN
The objective of this study was to investigate the immunolabelling of acetylated histones and histone desacetylase (HDAC) enzymes in canine soft tissue sarcomas (STSs) and to correlate them with histological and clinical features in order to identify possible prognostic and therapeutic targets in these neoplasms. Fifteen canine STS samples were evaluated and were submitted to immunohistochemistry for acetylated histones 3 (H3) and 4 (H4) and deacetylating enzymes (HDAC1, HDAC2 and HDAC6). Intense immunolabelling of H4 was seen in comparison with H3. A strong positive correlation was observed between the H3 intensity score and the number of mitotic figures (P = 0.004, r = 0.7). Intense immunolabelling of HDAC1 was found in comparison to the expression of HDAC2 and HDAC6 in the evaluated STSs. This finding suggests that HDAC1 may be a potential target for HDAC inhibitors in STSs in dogs.
Asunto(s)
Enfermedades de los Perros , Sarcoma , Animales , Perros , Histona Desacetilasas/metabolismo , Histonas/metabolismo , Inmunohistoquímica , Pronóstico , Sarcoma/veterinariaRESUMEN
Deficiency of 21-hydroxylase enzyme (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction and functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V, and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of CYP21A2 deficiency.
Asunto(s)
Genética de Población , Mutación/genética , Esteroide 21-Hidroxilasa/genética , Adolescente , Secuencia de Aminoácidos , Brasil , Preescolar , Simulación por Computador , Secuencia Conservada , Femenino , Humanos , Lactante , Cinética , Masculino , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/genética , Portugal , Reproducibilidad de los Resultados , Esteroide 21-Hidroxilasa/químicaRESUMEN
Native extracts from orange peels were obtained by a conventional method using acetone and, an alternative method using ionic liquid (1-butyl-3-methylimidazolium chloride ([C4mim]Cl)). The bioaccessibilities and cellular uptakes of carotenoids, esters and chlorophylls were evaluated, since the influence of esterification on bioaccessibility and bioavailability is not well established. For this, the extracts were emulsified, submitted to in vitro simulated digestion model according to the INFOGEST protocol, followed by uptake by Caco-2 cells. Compounds were separated, identified and quantified by HPLC-PDA-MS/MS. After digestion, 22.0% and 26.2% of the total carotenoids and 45.9% and 68.7% of the chlorophylls were bioaccessible from the acetone and [C4mim]Cl extracts, respectively. The bioaccessibilities of xanthophylls and carotenes were significantly higher than those of the mono- and diesters. The uptake by Caco-2 cells varied from 130.2 to 131.9 ng/mg cell protein for total carotenoids and from 243.8 to 234.2 ng/mg cell protein for chlorophylls in the acetone and [C4mim]Cl extracts, respectively. In general, xanthophylls and esters were better absorbed than carotenes.
Asunto(s)
Carotenoides/farmacocinética , Fraccionamiento Químico/métodos , Clorofila/farmacocinética , Citrus sinensis/química , Disponibilidad Biológica , Células CACO-2 , Carotenoides/análisis , Carotenoides/aislamiento & purificación , Clorofila/análisis , Clorofila/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Digestión , Ésteres/farmacocinética , Frutas/química , Humanos , Líquidos Iónicos/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacocinética , Espectrometría de Masas en Tándem , Xantófilas/análisis , Xantófilas/aislamiento & purificación , Xantófilas/farmacocinéticaRESUMEN
OBJECTIVES: The aim of this study was to establish the safety and efficacy of a novel multidrug lomustine-based chemotherapeutic protocol for cats with high-grade multicentric or mediastinal lymphoma, in an area endemic for feline leukemia virus (FeLV). METHODS: This prospective study included owned cats, diagnosed (cytologically) with multicentric or mediastinal lymphoma and treated with the LOPH (lomustine, vincristine [Oncovin; Antibióticos do Brasil], prednisolone and hydroxydaunorubicin [doxorubicin]) protocol. A complete blood count was performed before every chemotherapy session and any significant abnormalities recorded as possible related toxicities. Median survival time (MST) and disease-free interval were estimated by Kaplan-Meier curves. RESULTS: Twenty-one cats were included in this study. Nineteen (90.5%) tested positive for FeLV and were therefore considered to have persistent viremia. Complete response was reported in 81% (n = 17/21), while three had partial remission and one had no response. Seven cats finished the induction protocol within 20-31 weeks (23.1 ± 4.5; median 20) and all seven received a maintenance protocol. The MST (lymphoma-related survival) for the 21 cats was 214 days. The MST was 214 days for cats with mediastinal lymphoma (n = 13), but it was not reached for multicentric lymphoma (n = 8; P = 0.9). The MST of cats with persistent FeLV antigenemia was 171 days. Grade I anorexia and vomiting occurred in 19% of the cats (n = 4/21). Hematologic toxicity was found in 100% of the cats at some point during their treatment, but it was mostly grade I or II. Neutropenia, thrombocytopenia and anemia occurred in 16/21, 21/21 and 15/21 cats, respectively. CONCLUSIONS AND RELEVANCE: The LOPH protocol was well tolerated by cats with lymphoma and persistent FeLV viremia, and resulted in a better MST than similar studies with other protocols. Novel studies and controlled trials are necessary in order to evaluate the efficacy of different protocols according to the lymphoma subtype, anatomic form and FeLV status.
Asunto(s)
Enfermedades de los Gatos , Leucemia Felina , Linfoma , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Virus de la Leucemia Felina , Leucemia Felina/tratamiento farmacológico , Leucemia Felina/epidemiología , Linfoma/tratamiento farmacológico , Linfoma/veterinaria , Estudios Prospectivos , VincristinaRESUMEN
Cutaneous lymphoma is histologically classified in epitheliotropic and non-epitheliotropic, the first showing higher incidence in dogs, and the second, in cats. Non-epitheliotropic lymphoma presents lymphocyte aggregates in the dermis and subcutaneous tissue, however cutaneous annexes are not infiltrated. It is usually more aggressive than epitheliotropic lymphomas. The aim of this study was to report a case of non-epitheliotropic lymphoma in a 9-year-old, female, English Bulldog presented with non-ulcerated skin nodules adhered to deep tissues. Microscopic and immunophenotypic features supported the diagnosis of non-epitheliotropic large T-cell lymphoma. Treatment was initiated with modification of the LOPP protocol, replacing procarbazine by dacarbazine (600 mg/m²) for up to six cycles, with a three-month survival. In the 11th week of treatment, after recurrent episodes of vomiting and diarrhea, abdominal ultrasound was performed and revealed an infiltrative mass in the stomachs greater curvature topography, showing an expansive and accentuated increase in one week, when euthanasia was elected.
Asunto(s)
Animales , Gatos , Perros , Perros/lesiones , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/veterinariaRESUMEN
Cutaneous lymphoma is histologically classified in epitheliotropic and non-epitheliotropic, the first showing higher incidence in dogs, and the second, in cats. Non-epitheliotropic lymphoma presents lymphocyte aggregates in the dermis and subcutaneous tissue, however cutaneous annexes are not infiltrated. It is usually more aggressive than epitheliotropic lymphomas. The aim of this study was to report a case of non-epitheliotropic lymphoma in a 9-year-old, female, English Bulldog presented with non-ulcerated skin nodules adhered to deep tissues. Microscopic and immunophenotypic features supported the diagnosis of non-epitheliotropic large T-cell lymphoma. Treatment was initiated with modification of the LOPP protocol, replacing procarbazine by dacarbazine (600 mg/m²) for up to six cycles, with a three-month survival. In the 11th week of treatment, after recurrent episodes of vomiting and diarrhea, abdominal ultrasound was performed and revealed an infiltrative mass in the stomachs greater curvature topography, showing an expansive and accentuated increase in one week, when euthanasia was elected.(AU)
Asunto(s)
Animales , Gatos , Perros , Perros/lesiones , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/veterinariaRESUMEN
Diochus Erichson is a worldwide rove beetle genus with species found in forest floor litter. Three species of Diochus were recently collected in northern Brazil, one of them considered as new and herein described. Within Diochus nanus-group, D. cleidecostae sp. nov. differs from D. apicipennis Cameron, D. nanus Erichson and D. perplexus Cameron by the aedeagus with clearing trifurcate apex of parameres; and differs from D. parvulus Kraatz by the three apical long setae of parameres distributed on ventral and dorsal lobes. A previous key to the D. nanus-group is updated to include the new species. Here we also report for the first time D. santacatarinae Irmler and D. parvulus from Pará state, Brazil. Finally, a discussion about the sexual dimorphism on sternum VIII is also provided for the genus.
Asunto(s)
Animales , Escarabajos/anatomía & histología , Escarabajos/clasificación , Caracteres Sexuales , Esternón , Ecosistema AmazónicoRESUMEN
Diochus Erichson is a worldwide rove beetle genus with species found in forest floor litter. Three species of Diochus were recently collected in northern Brazil, one of them considered as new and herein described. Within Diochus nanus-group, D. cleidecostae sp. nov. differs from D. apicipennis Cameron, D. nanus Erichson and D. perplexus Cameron by the aedeagus with clearing trifurcate apex of parameres; and differs from D. parvulus Kraatz by the three apical long setae of parameres distributed on ventral and dorsal lobes. A previous key to the D. nanus-group is updated to include the new species. Here we also report for the first time D. santacatarinae Irmler and D. parvulus from Pará state, Brazil. Finally, a discussion about the sexual dimorphism on sternum VIII is also provided for the genus.(AU)
Asunto(s)
Animales , Escarabajos/anatomía & histología , Escarabajos/clasificación , Caracteres Sexuales , Esternón , Ecosistema AmazónicoRESUMEN
Abstract Diochus Erichson is a worldwide rove beetle genus with species found in forest floor litter. Three species of Diochus were recently collected in northern Brazil, one of them considered as new and herein described. Within Diochus nanus-group, D. cleidecostae sp. nov. differs from D. apicipennis Cameron, D. nanus Erichson and D. perplexus Cameron by the aedeagus with clearing trifurcate apex of parameres; and differs from D. parvulus Kraatz by the three apical long setae of parameres distributed on ventral and dorsal lobes. A previous key to the D. nanus-group is updated to include the new species. Here we also report for the first time D. santacatarinae Irmler and D. parvulus from Pará state, Brazil. Finally, a discussion about the sexual dimorphism on sternum VIII is also provided for the genus.
RESUMEN
PURPOSE: To assess the prevalence of macular abnormalities not suspected by the biomicroscopic fundus examination and identified only by macular optical coherence tomography (OCT) in the preoperative evaluation for cataract surgery in a large series of Brazilian patients. SETTING: Private practice, Recife, Brazil. DESIGN: Retrospective case series. METHODS: All eyes that had cataract surgery by the same physician between August 2014 and July 2016 were eligible. Excluded were eyes with a previous diagnosis of macular abnormalities, with a suspicious biomicroscopic fundus examination, and without OCT results. Based on the preoperative macular OCT, patients were divided into the following 2 groups: those with a normal OCT and those with an abnormal OCT. RESULTS: Nine hundred fifty-two eyes (614 patients) were included in the study. Macular OCT identified abnormalities in 47 eyes (4.9%) of 44 patients (7.2%). Thirty-one eyes (3.3%) had epiretinal membrane, 7 (0.7%) had age-related macular degeneration, 4 (0.4%) had intraretinal cysts, 4 (0.4%) had a lamellar hole, and 1 (0.1%) had a macular hole. Patients with an abnormal OCT had a statistically significant higher mean age (P = .004). CONCLUSION: In the preoperative evaluation for cataract surgery in Brazilian patients, 7.2% of those with a normal biomicroscopic fundus examination had macular abnormalities that were identified only by OCT.
Asunto(s)
Catarata/complicaciones , Mácula Lútea/patología , Enfermedades de la Retina/epidemiología , Tomografía de Coherencia Óptica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Extracción de Catarata , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Prevalencia , Enfermedades de la Retina/etiología , Estudios Retrospectivos , Microscopía con Lámpara de Hendidura , Agudeza Visual , Adulto JovenRESUMEN
Chalcones are valuable structures for drug discovery due to their broad bioactivity spectrum. In this study, we evaluated 20 synthetic chalcones against estrogen-receptor-positive breast cancer cells (MCF-7 line) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 line). Antiproliferative screening by MTT assay resulted in two most active compounds: 2-fluoro-4'-aminochalcone (11) and 3-pyridyl-4'-aminochalcone (17). Their IC50 values ranged from 13.2 to 34.7 µM against both cell lines. Selected chalcones are weak basic compounds and maintained their antiproliferative activity under acidosis conditions (pH 6.7), indicating their resistance to ion-trapping effect. The mode of breast cancer cells death was investigated and chalcones 11 and 17 were able to induce apoptosis rather than necrosis in both lines. Antiproliferative target investigations with MCF-7 cells suggested 11 and 17 upregulated p53 protein expression and did not affect Sp1 protein expression. Future studies on chalcones 11 and 17 can define their in vivo therapeutic potential.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Chalconas/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Chalconas/síntesis química , Chalconas/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Células MCF-7 , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
BACKGROUND: The angiogenesis process is regulated by many factors, such as Hypoxia-Inducible Factor-1 (HIF-1) and Vascular Endothelial Growth Factor (VEGF). Metformin has demonstrated its ability to inhibit cell growth and the LY294002 is the major inhibitor of PI3K/AKT/mTOR pathway that has antiangiogenic properties. METHODS: Canine mammary tumor cell lines CMT-U229 and CF41 were treated with metformin and LY294002. Cell viability, protein and gene expression of VEGF and HIF-1 were determined in vitro. For the in vivo study, CF41 cells were inoculated in female athymic nude mice treated with either metformin or LY294002. The microvessel density by immunohistochemistry for CD31 as well as the gene and protein expression of HIF-1 and VEGF were evaluated. RESULTS: The treatment with metformin and LY294002 was able to reduce the cellular viability after 24 hours. The protein and gene expression of HIF-1 and VEGF decreased after treatment with metformin and LY294002. In the in vivo study, there was a decrease in tumor size, protein and gene expression of HIF-1 and VEGFA, in addition to the decreasing of CD31 expression after all treatments. CONCLUSION: Our results demonstrate the effectiveness of metformin and LY294002 in controlling the angiogenesis process in mammary tumors by VEGF and HIF-1, the most important angiogenic markers.