RESUMEN
Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.
Asunto(s)
Hipoxia/inmunología , Antígenos Comunes de Leucocito/metabolismo , Macrófagos/inmunología , Monoéster Fosfórico Hidrolasas/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Diferenciación Celular , Movimiento Celular , Células Cultivadas , Dimerización , Femenino , Antígenos Comunes de Leucocito/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Células Mieloides/inmunología , Monoéster Fosfórico Hidrolasas/genética , Factor de Transcripción STAT3/genética , Ácidos Siálicos/metabolismo , Microambiente TumoralRESUMEN
BACKGROUND: Radiation associated angiosarcoma (RAAS) of the breast is a rare, but lethal complication of breast conserving surgery (BCS). Early recognition and knowledge of treatment modalities is imperative for successful treatment. We present the experience of a large community cancer center, with review of the literature. METHODS: The Christiana Care Department of Pathology and the Helen F. Graham Cancer Center and Research Institute databases were queried from 2001-2011 and 2011-2015 respectively for soft tissue neoplasms of the breast. A total of 2,153 patients with diagnosis of malignant neoplasm of the breast not otherwise specified (NOS) were identified. There were seven cases of RAAS identified. RESULTS: Seven patients with RAAS were identified. Average age at presentation was 70 years with a range of 58-87. Time from radiation therapy to diagnosis was 8.5 years with a range of 4.0 years to 14.9 years. Five of seven patients presented with skin lesions, all with varying clinical signs. Clinical lymphedema was not identified in any of these patients. CONCLUSION: Radiation associated angiosarcoma of the breast is an aggressive tumor with poor prognosis. Larger studies are needed to evaluate adjuvant treatments; however the small number of cases makes this prohibitive. Genetic testing and potentially targeted therapies are emerging as options for treatment and prevention of this complicated disease process.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Hemangiosarcoma/diagnóstico , Neoplasias Inducidas por Radiación/diagnóstico , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Femenino , Amplificación de Genes , Hemangiosarcoma/terapia , Humanos , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/terapia , Proteínas Proto-Oncogénicas c-myc/genética , Enfermedades Raras , Estudios RetrospectivosRESUMEN
In the USA, 80% of patients with breast cancer are treated by community breast surgeons. NCDB data indicate that there are only small differences in outcomes between lower volume cancer programs and higher volume programs. There is some evidence that breast cancer patients of high-volume breast focused surgeons may have improved outcomes. This article discusses the challenges community breast surgeons face and some ways that the quality of care could be monitored and improved. Quality reporting programs of the Commission on Cancer and Mastery of Breast Surgery Program of the American Society of Breast Surgeons are recommended as tools to track and improve outcomes in breast cancer care.
Asunto(s)
Neoplasias de la Mama/cirugía , Redes Comunitarias , Atención a la Salud , Evaluación de Resultado en la Atención de Salud , Pautas de la Práctica en Medicina , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Mastectomía , Indicadores de Calidad de la Atención de Salud , Tasa de SupervivenciaRESUMEN
PURPOSE: We compared patients undergoing partial breast irradiation (PBI) with the MammoSite applicator (Cytyc Corp., Marlborough, MA) to a similar group of patients who underwent whole breast irradiation with external beam radiotherapy. METHODS AND MATERIALS: Stage 0-IIA breast cancer patients satisfying American Brachytherapy Society selection criteria and receiving accelerated PBI with the MammoSite system (n=100) were compared for toxicities with similarly staged patients receiving whole breast irradiation using tangential portals (n=100). The MammoSite applicator treatment was prescribed to a total dose of 34 Gy. External beam doses generally ranged from 60 to 66 Gy. RESULTS: Based on common toxicity criteria scores for acute toxicities, MammoSite patients experienced less cutaneous toxicity, fatigue, and breast pain and had higher Karnofsky performance status scores during the acute period than external beam patients but experienced more seroma pain during followup. These results were both statistically significant and clinically meaningful. CONCLUSIONS: In our institutional experience, PBI using the MammoSite applicator produces less acute toxicity than external beam radiotherapy of the whole breast but is associated with an increased incidence of seroma pain. The rate of disease recurrence in both cohorts was low.