RESUMO
A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.
Assuntos
Transplante de Córnea , Mitomicina , Humanos , Mitomicina/uso terapêutico , Transplante de Córnea/métodos , Doenças da Córnea/cirurgia , Doenças da Córnea/tratamento farmacológico , Neoplasias Oculares/cirurgia , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Resultado do Tratamento , Masculino , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Antibióticos Antineoplásicos/uso terapêuticoRESUMO
The present study investigated the effect of adding allopathic doxorubicin (DOX 0.3⯵g/mL), the vehicle of ultradiluted/dynamized doxorubicin (0.2â¯% ethanol), different dynamizations of ultradiluted/dynamized doxorubicin (DOX 6CH, DOX 12CH and DOX 30CH), both in the absence or presence of chemical stress induced by doxorubicin at 0.3⯵g/mL on follicular survival and activation, antioxidant capacity of the medium, Catalase activity (CAT), production of reactive protein thiol, maintenance of type I and III collagen fibers and accumulation of lipofuscin in porcine ovarian tissue cultured in vitro for 48â¯hours. To do this, part of the ovarian tissue fragments was fixed for the uncultured control and the rest were cultured in: MEM (cultured control), DOX 0.3⯵g/mL, Ethanol, DOX 6CH, DOX 12CH, DOX 30CH, DOX (0.3⯵g/mL) + DOX 6CH, DOX (0.3⯵g/mL) + DOX 12CH, DOX (0.3⯵g/mL) + DOX 30CH treatments. The results showed that, in general, ultradiluted/dynamized doxorubicin (DOX 6CH, DOX 12CH and DOX 30CH) mitigated the toxic effect of allopathic doxorubicin (0.3⯵g/mL) on the morphology of preantral follicles, the content of type I and III collagen fibers, and the production of lipofuscin in the tissue. However, only DOX (0.3⯵g/mL) + DOX 6CH attenuated the oxidative stress induced by DOX (0.3⯵g/mL), maintaining adequate CAT activity that was similar to the uncultured control. Additionally, when the three isolated ultradiluted/dynamized doxorubicin were considered, only DOX 12CH increased the reduced thiol levels compared to the uncultured control and MEM. In conclusion, supplementing the culture medium with ultradiluted/dynamized DOX (DOX 6CH, DOX 12CH and DOX 30CH) attenuated the toxicity induced by allopathic doxorubicin during the in vitro culture of pig preantral follicles enclosed in ovarian tissue.
Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Folículo Ovariano , Animais , Doxorrubicina/toxicidade , Feminino , Suínos , Antibióticos Antineoplásicos/toxicidade , Folículo Ovariano/efeitos dos fármacos , Catalase/metabolismo , Técnicas de Cultura de Tecidos , Lipofuscina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Colágeno Tipo I/metabolismo , Ovário/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Colágeno Tipo III/metabolismoRESUMO
BACKGROUND: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. OBJECTIVE: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. METHODS: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. RESULTS: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. CONCLUSION: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis.
FUNDAMENTO: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. OBJETIVO: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. MÉTODOS: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. RESULTADOS: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. CONCLUSÃO: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1.
Assuntos
Apoptose , Doxorrubicina , MicroRNAs , Miócitos Cardíacos , RNA Longo não Codificante , Humanos , Doxorrubicina/farmacologia , RNA Longo não Codificante/genética , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Antibióticos Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Reprodutibilidade dos Testes , Western Blotting , Citometria de Fluxo , RNA Endógeno CompetitivoRESUMO
In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.
Assuntos
Doxorrubicina , Galactose , Mananas , Nanoconjugados , Doxorrubicina/farmacologia , Doxorrubicina/química , Mananas/química , Mananas/farmacologia , Galactose/química , Galactose/análogos & derivados , Humanos , Nanoconjugados/química , Concentração de Íons de Hidrogênio , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects.
Assuntos
Amantadina , Sobrevivência Celular , Dano ao DNA , Doxorrubicina , Humanos , Doxorrubicina/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Amantadina/farmacologia , Amantadina/toxicidade , Amantadina/análogos & derivados , Dano ao DNA/efeitos dos fármacos , Mutagênicos/toxicidade , Antibióticos Antineoplásicos/toxicidade , Testes de MutagenicidadeRESUMO
BACKGROUND: The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and mortality rates due to cardiovascular (CV) complications. OBJECTIVES: To determine the cardiovascular profile of pediatric patients treated with anthracyclines at a cancer center in Brazil and the incidence of CV complications. METHODS: The following data were collected from the medical records of patients of both sexes, aged younger than 19 years - frequency and form of clinical presentation of general CV complications (G1) and CV complications related to ventricular dysfunction (G2) - and correlated with risk factors, age range and vital status, cardiovascular and cardioprotective medications. A p<0.05 was considered statistically significant. RESULTS: A total of 326 patients were included, 214 (65.6%) were younger than 10 years and 192 (58.9%) of male sex. G1 complications occurred in 141 (43.3%) patients, and the most frequent was systemic arterial hypertension; G2 complications occurred in 84 patients (25.8%). Cumulative dose (CD) of anthracyclines > 250mg/m2 was used in 26.7% of patients and the association of G2 complications with this CD was not statistically significant (p=0.305; OR=1.330 and [95% CI = 0.770- 2.296]). The most used cardiac medications were diuretics (34.7% of patients). CONCLUSIONS: In accordance with literature, the study showed a high incidence of CV complications in the treatment of children and adolescents with cancer, with general CV complications as the most prevalent.
FUNDAMENTO: A introdução das antraciclinas no tratamento do câncer infantojuvenil propiciou um aumento significativo na sobrevida, mas também nas taxas de morbimortalidade devido às complicações cardiovasculares (CVs). OBJETIVOS: Conhecer o perfil cardiológico de pacientes pediátricos tratados com antraciclinas em um centro oncológico no Brasil e a incidência das complicações CVs. MÉTODOS: Foram coletados, de prontuários de pacientes de ambos os sexos com idade até 19 anos frequência e forma de apresentação clínica das complicações CVs Gerais (G1) e relacionadas à Disfunção Ventricular (G2) e correlacionados com fatores de risco, faixa etária e estado vital, medicações cardiológicas e cardioprotetoras. Um valor de p < 0,05 foi considerado significativo. RESULTADOS: Foram incluídos 326 pacientes, destes, 214 (65,6%) eram menores de 10 anos e 192 (58,89%) do sexo masculino. As complicações do G1 ocorreram em 141 (43,3%) pacientes e a mais frequente foi a hipertensão arterial sistêmica; as complicações do G2 ocorreram em 84 pacientes (25,76%). Uma Dose Cumulativa (DC) das antraciclinas > 250mg/m2 foi usada em 26,7% dos pacientes e a associação de complicações do G2 com essa DC não mostrou significância estatística (p=0,305; RC=1,330 e [95% IC= 0,770- 2,296]). As medicações cardiológicas mais usadas foram os diuréticos em 34,7% dos pacientes. CONCLUSÕES: O estudo mostrou, como na literatura, uma alta incidência de complicações CVs no tratamento do câncer infantojuvenil, sendo as do G1 as mais frequentes.
Assuntos
Antraciclinas , Doenças Cardiovasculares , Humanos , Masculino , Feminino , Criança , Antraciclinas/efeitos adversos , Brasil/epidemiologia , Adolescente , Pré-Escolar , Incidência , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Lactente , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Estudos Retrospectivos , Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Distribuição por Sexo , Adulto JovemRESUMO
BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.
Assuntos
Biomarcadores , Neoplasias da Mama , Cardiotoxicidade , Doxorrubicina , Mioglobina , Troponina I , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Estudos Prospectivos , Troponina I/sangue , Doxorrubicina/efeitos adversos , Cardiotoxicidade/etiologia , Pessoa de Meia-Idade , Biomarcadores/sangue , Mioglobina/sangue , Adulto , Antibióticos Antineoplásicos/efeitos adversos , Peptídeo Natriurético Encefálico/sangue , Idoso , Creatina Quinase Forma MB/sangue , Estudos Longitudinais , Antraciclinas/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Valor Preditivo dos TestesRESUMO
While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.
Assuntos
Caquexia , Doxorrubicina , Fragilidade , Camundongos Endogâmicos C57BL , Músculo Esquelético , Sarcopenia , Animais , Doxorrubicina/efeitos adversos , Caquexia/induzido quimicamente , Caquexia/etiologia , Sarcopenia/induzido quimicamente , Sarcopenia/patologia , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Masculino , Força Muscular/efeitos dos fármacos , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Redução de Peso/efeitos dos fármacos , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/toxicidadeRESUMO
OBJECTIVE: The objective of this study was to investigate the impact of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in osteosarcoma patients and analyze the factors influencing this effect. METHODS: A retrospective study was conducted on 165 osteosarcoma patients admitted to our hospital from January 2020 to December 2022. Based on the chemotherapy regimen, the patients were divided into two groups: the control group (n = 62) treated with Cisplatin and cyclophosphamide, and the observation group (n = 103) treated with Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline). The general records of both groups were analyzed, and left ventricular ejection fraction (LVEF) was evaluated through echocardiography before and after chemotherapy. Blood cTnT and CK-MB levels were measured using immunoluminescence. The incidence of adverse reactions during chemotherapy was also analyzed. Univariate analysis was performed to identify patients with cardiotoxic events, and multiple logistic regression analysis was done to study the effects of Doxorubicin, Epirubicin, Liposomal Doxorubicin, and their dosages on cardiotoxicity in patients. RESULTS: The general records between the two groups showed no significant differences (P > 0.05). However, at the fourth cycle of chemotherapy, the observation group exhibited a lower LVEF (P < 0.05), and a higher percentage of LVEF decrease compared to the control group (P < 0.05). Moreover, the observation group had higher levels of blood cTnT and CK-MB (P < 0.05). The incidence of cardiotoxicity in the observation group was also higher (P < 0.05), but no significant differences were seen in other adverse reaction rates (P > 0.05). The occurrence of cardiotoxicity was found to be related to the choice and dosage of chemotherapy drugs (P < 0.05), but not significantly correlated with age, sex, and mediastinal irradiation in patients (P > 0.05). Furthermore, the use of Doxorubicin, Epirubicin, and Liposomal Doxorubicin in chemotherapy, as well as an increase in their dosages, was found to elevate the risk of cardiotoxicity in osteosarcoma patients (P < 0.05). However, age, sex, and mediastinal radiation were not significantly associated with cardiotoxicity in osteosarcoma patients (P > 0.05). CONCLUSION: We demonstrated that Doxorubicin, Epirubicin, Liposomal Doxorubicin (Anthracycline), and other drugs adversely affected cardiac function in osteosarcoma patients, increasing the risk of cardiac toxicity. Therefore, close monitoring of cardiac function during chemotherapy is crucial, and timely adjustments to the chemotherapy regimen are necessary. In addition, rational control of drug selection and dosage is essential to minimize the occurrence of cardiac toxicity.