RESUMEN
Sulf-2 has been identified as a putative target for anticancer therapies. Here we report the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S). Trisulfated disaccharide inhibitor IdoA(2S)-GlcNS(6Sulfamate) demonstrated potent Sulf-2 inhibition. The IC50 value was determined to be 39.8 µM ± 18.3, which is comparable to a tetrasaccharide inhibitor of HSulf-1 reported in the literature. We propose that the disaccharide IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of the Sulfs.
Asunto(s)
Heparitina Sulfato , Oligosacáridos , Heparitina Sulfato/farmacología , Oligosacáridos/farmacología , Disacáridos/farmacología , SulfotransferasasRESUMEN
AIM: Feasibility-reliability control of Telemedicine Systems (TS) integrated with Multimedia Systems (MS) and Artificial intelligence (AI) for remote e-Multidisciplinary Oncology Conference in Breast Cancer. MATERIAL AND METHODS: Forty (n1=40) patients suffering from breast surgical oncology malignant (n2=32) and non-malignant (n3=8) diseases classified to seven categories: Nipple Discharge, Dominant Breast Mass, Occult Breast Lesion, Early Breast Carcinoma, Advanced Breast Carcinoma, Recurrent Breast Carcinoma) and treated clinically with the standard diagnostic (Mammography, US, MRI, Cytology, Pathology, BRCA1/2 Mutation Predisposition and Breast Cancer Risk Analysis) surgical, auxiliary therapeutic methods. Then clinical decisions compared to those proposed remotely by the virtual AI supported e-Oncology Conference for each patient. RESULTS: In four (n4=4) out of forty patients (TS, MS and AI) supported decision making and surgical treatment proposal including postoperative Radiotherapy proposal was not as clear as expected. Non-output answer for non-malignant breast pathologies (n3=8) was accurately indicated by (MS and AI). Mean accuracy of (TS, MS and AI) for: 1.Surgical Operative Planning including Rad=94.1%, 2.Chem=96.8%, 3.Horm=96.7% [In 95%, (Confidence interval: 85-99%)]. CONCLUSION: High feasibility-reliability of the virtual AI supported e-Multidisciplinary Oncology Conference for remote decision making and surgical planning and for optimum outcomes in Breast Cancer treatment makes it a clinical necessity especially for the periphery of Hellas.
Asunto(s)
Neoplasias de la Mama , Inteligencia Artificial , Neoplasias de la Mama/terapia , Femenino , Humanos , Recurrencia Local de Neoplasia , Reproducibilidad de los Resultados , TecnologíaRESUMEN
Acute myeloid leukemia (AML) is the most aggressive type of blood cancer, and there is a continued need for new treatments that are well tolerated and improve long-term survival rates in patients. Induction of differentiation has emerged as a promising alternative to conventional cytotoxic chemotherapy, but known agents lack efficacy in genetically distinct patient populations. Previously, we established a phenotypic screen to identify small molecules that could stimulate differentiation in a range of AML cell lines. Utilising this strategy, a 1,5-dihydrobenzo[e][1,4]oxazepin-2(3H)-one hit compound was identified. Herein, we report the hit validation in vitro, structure-activity relationship (SAR) studies and the pharmacokinetic profiles for selected compounds.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Diferenciación Celular/efectos de los fármacos , Antineoplásicos/síntesis química , Línea Celular Tumoral , Células Cultivadas , Técnicas de Química Sintética , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Leucemia Mieloide Aguda , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Intracystic papillary carcinoma of the male breast represents an extremely rare entity that accounts for less than 1% of all malignancies, and histologically may range from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. This report presents the case of a 61-year-old Caucasian man who presented with a 5-year history of a centrally located painless swelling of his right breast with occasional nipple discharge. Triple assessment was very helpful in establishing the diagnosis. Treatment included a mastectomy and hormonal therapy because the neoplasm expressed hormone receptors. Although male breast carcinomas tend to behave more aggressively than their female counterparts, the prognosis of this neoplasm is excellent.