RESUMO
DNA chains with sequential guanine (G) repeats can lead to the formation of G-quadruplexes (G4), which are found in functional DNA and RNA regions like telomeres and oncogene promoters. The development of molecules with adequate structural features to selectively stabilize G4 structures can counteract cell immortality, highly described for cancer cells, and also downregulate transcription events underlying cell apoptosis and/or senescence processes. We describe here, the efficiency of four highly charged porphyrins-phosphonium conjugates to act as G4 stabilizing agents. The spectrophotometric results allowed to select the conjugates P2-PPh3 and P3-PPh3 as the most promising ones to stabilize selectively G4 structures. Molecular dynamics simulation experiments were performed and support the preferential binding of P2-PPh3 namely to MYC and of P3-PPh3 to KRAS. The ability of both ligands to block the activity of Taq polymerase was confirmed and also their higher cytotoxicity against the two melanoma cell lines A375 and SK-MEL-28 than to immortalized skin keratinocytes. Both ligands present efficient cellular uptake, nuclear co-localization and high ability to generate 1O2 namely when interacting with G4 structure. The obtained data points the synthesized porphyrins as promising ligands to be used in a dual approach that can combine G4 stabilization and Photodynamic therapy (PDT).
RESUMO
Melanoma is a drug-resistant cancer, representing a serious challenge in cancer treatment. Dacarbazine (DTIC) is the standard drug in metastatic melanoma treatment, despite the poor results. Hyperthermia has been proven to potentiate chemotherapy. Hence, this work analyzed the combined action of hyperthermia and DTIC on A375 and MNT-1 cell lines. First, temperatures between 40 °C and 45 °C were tested. The effect of DTIC on cell viability was also investigated after exposures of 24, 48, and 72 h. Then, cells were exposed to 43 °C and to the respective DTIC IC10 or IC20 of each time exposure. Overall, hyperthermia reduced cell viability, however, 45 °C caused an excessive cell death (>90%). Combinational treatment revealed that hyperthermia potentiates DTIC's effect, but it is dependent on the concentration and temperature used. Also, it has different mechanisms from the treatments alone, delaying A375 cells at the G2/M phase and MNT-1 cells at the S and G2/M phases. Intracellular reactive oxygen species (ROS) levels increased after treatment with hyperthermia, but the combined treatment showed no additional differences. Also, hyperthermia highly increased the number of A375 early apoptotic cells. These results suggest that combining hyperthermia and DTIC should be more explored to improve melanoma treatment.
Assuntos
Hipertermia Induzida , Melanoma , Linhagem Celular Tumoral , Sobrevivência Celular , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Introducción: La mayoría de los pacientes con enfermedad renal crónica terminal en hemodiálisis desarrollan hiperparatiroidismo secundario. Algunas veces este tipo de hiperparatiroidismo secundario suele ser severo y refractario al tratamiento médico, inclusive algunos desarrollarán hiperparatiroidismo terciario, el tratamiento de ambas situaciones suele ser la paratiroidectomía subtotal o total. Reporte de Caso: Presentamos el caso de un paciente de 29 años, con enfermedad renal terminal en hemodiálisis durante 13 años, quien desarrolló hiperparatiroidismo terciario por lo que fue sometido a paratiroidectomía subtotal con autotrasplante de media glándula; el estudio patológico informó la presencia de un carcinoma de paratiroides en una de las cuatro glándulas paratiroides extirpadas. Conclusión: El carcinoma de paratiroides es una neoplasia rara que causa hiperparatiroidismo primario en menos de 1% de todos los casos, y se ha reportado en algunos pacientes operados por hiperparatiroidismo terciario.
Background: Most patients with terminal chronic kidney disease on hemodialysis develop secondary hyperparathyroidism. Sometimes this type of secondary hyperparathyroidism becomes severe and refractory to medical treatment, some will even develop tertiary hyperparathyroidism, the treatment of both situations is usually subtotal or total parathyroidectomy. Case Report: We present the case of a 29-year-old patient with end-stage kidney disease on hemodialysis for 13 years, who developed tertiary hyperparathyroidism, for which he underwent subtotal parathyroidectomy with half gland autotransplantation; the pathological study reported the presence of a parathyroid carcinoma in one of the four excised parathyroid glands. Conclusion: Parathyroid carcinoma is a rare neoplasm that causes primary hyperparathyroidism in less than 1% of all cases, and has been reported in some patients operated on for the development of tertiary hyperparathyroidism.
RESUMO
Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.
Assuntos
Doxorrubicina/farmacologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Hipertermia Induzida/métodos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Melanoma/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/metabolismoRESUMO
Staphylococcus aureus is responsible for skin and soft tissue infections. Having in mind increased antibiotic resistance, in this study the efficacy of antimicrobial photodynamic therapy (aPDT) with a porphyrinic formulation (FORM) as photosensitizer (PS) to photoinactivate methicillin-resistant Staphylococcus aureus (MRSA) on skin was evaluated. Potassium iodide (KI) and iodopovidone (PVP-I) were also tested in combination with FORM as potentiator agents of FORM efficacy. The aPDT protocol was first developed in Phosphate Buffered Saline (PBS, in vitro). Porcine skin was artificially contaminated with MRSA (ex vivo) and treated with FORM, FORM + KI or FORM + PVP-I under white light. The in vitro results showed that FORM was effective to inactivate MRSA. A substantial reduction in the irradiation time, when compared to FORM alone, was observed for FORM + KI and FORM + PVP-I combinations. On skin, reductions in MRSA survival of 3.1 Log10 colony forming units (CFU) mL-1 were observed with FORM at 50 µM. Although the combined action of FORM + KI and FORM + PVP-I potentiated the aPDT efficacy in vitro, this was not observed ex vivo. Overall, the results showed that aPDT using FORM, even without coadjutants, is a promising approach for MRSA inactivation on skin.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , SuínosRESUMO
Resumen:
Introducción: a nivel mundial, el cáncer de mama ocupa el primer lugar de muerte por neoplasia maligna. Para el 2030, representará aproximadamente 850 000 muertes de mujeres en edad productiva y más del 85 % estará en un rango de 29 a 69 años de edad. Para las mujeres con cáncer de mama sometidas a mastectomía y que pasaron por quimioterapia y/o radioterapia, el cuidado que la enfermera debe ofrecer es imprescindible.
Objetivo: describir el conocimiento del personal de enfermería sobre los cuidados postoperatorios a la mujer con mastectomía.
Metodología: estudio transversal descriptivo con 200 enfermeras y enfermeros de oncología; se diseñó un instrumento estructurado con ocho apartados y 29 reactivos; la prueba piloto se realizó en 10 % de la muestra y se determinó la confiabilidad del instrumento mediante alfa de cronbach. El análisis fue descriptivo.
Resultados: el nivel de conocimiento sobre los cuidados de la paciente postoperada de mastectomía fue excelente (34 %) y bueno (50.5 %). Sin embargo, en los rubros de alimentación (47 %), vestido (37.5 %) y autoexploración de mama (56 %) no fue satisfactorio.
Conclusiones: El seguimiento del personal de enfermería en el cuidado de la mujer postoperada de mastectomía es fundamental para la recuperación, por ello es relevante que la orientación sea sistematizada en rubros específicos de alimentación, vestido y autoexploración de mama.
Abstract:
Introduction: Worldwide, breast cancer is the leading cause of death from maligrant neoplasms. In 2030, it will represent approximately 850 000 deaths of women in working age, and 85 % of those patients will be aged between 29 and 69 years. For women with breast cancer undergoing a mastectomy and those who went through chemotherapy and/or radiotherapy, the care that the nurse must provide is essential.
Objective: To describe the knowledge of nurses on postoperative care to women with mastectomy. Methodology: A descriptive cross-sectional study of 200 oncology nurses was carried out; a structured instrument with eight points and 29 test items was designed; the pilot test was performed in 10 % of the sample, and the reliability of the instrument was stablished by using cronbach's alpha. Results: The level of knowledge about post-op patient care was: excellent (34 %) and good (50.5 %). However, in the areas of food (47 %), clothing (37.5 %) and breast self-examination (56 %), the knowledge was not satisfactory.
Conclusions: Monitoring of nurses during the care of post-op mastectomized women is essential for recovery; thereby, it is important to systematize the training in specific items of food, clothing and breast self-examination.