A rare etiology of a large tumoral mass of the breast - Case report primary leiomyosarcoma and osteosarcoma of the breast.

Breast sarcomas are a rare group of malignant tumors accounting for less than 1% of all malignant neoplasms of the breast and fewer than 5% of all sarcomas. We report a case of an 87-year-old caucasian female who recurred to the emergency department with complaints of a painful mass of the left breast with purulent discharge. Observation revealed a volumous mass in the inferior quadrants of the breast, ill defined, with petrous consistency, areas of necrosis, and inflammatory signs. She was admitted to Surgery ward for further study and therapy of a probable inflammatory tumor of the breast. Magnetic resonance image was obtained, raising suspicion on papillary carcinoma and classified the breast as BIRADS5. Microbiological and cytological exams of the exudate were negative. An incisional biopsy of the tumoral mass was also obtained, and the patient discharged while waiting for surgery. Histological exam and immunohistochemical essay were compatible with leiomyosarcoma. Left mastectomy was performed and the patient was discharged with no morbidities on the 5th day after surgery. Histological exam of mastectomy piece showed a metaplastic carcinoma, with osteosarcomatous and focal leiomyosarcomatous differentiation. The lesion was classified as pT4N0M0 and subsequent radiotherapy was performed. Twenty months after surgery the patient was being followed-up on Oncology and Senology consultations and remained asymptomatic. Consensus on ideal management of this diseases is still on debate. Some authors defend the treatment of this entity in a similar way to sarcoma of the breast. More studies are needed to better understand this entity.

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles.

Neurogenic niches constitute a powerful endogenous source of new neurons that can be used for brain repair strategies. Neuronal differentiation of these cells can be regulated by molecules such as retinoic acid (RA) or by mild levels of reactive oxygen species (ROS) that are also known to upregulate RA receptor alpha (RARα) levels. Data showed that neural stem cells from the subventricular zone (SVZ) exposed to blue light (405nm laser) transiently induced NADPH oxidase-dependent ROS, resulting in ß-catenin activation and neuronal differentiation, and increased RARα levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis both in vitro and in vivo, while offering a temporal and spatial control of RA release. In conclusion, this combinatory treatment offers great advantages to potentiate neuronal differentiation, and provides an innovative and efficient application for brain regenerative therapies. STATEMENT OF SIGNIFICANCE: Controlling the differentiation of stem cells would support the development of promising brain regenerative therapies. Blue light transiently increased reactive oxygen species, resulting in neuronal differentiation and increased retinoic acid receptor (RARα) levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis, while offering a temporal and spatial control of RA release. In this sense, our approach relying on the modulation of endogenous stem cells for the generation of new neurons may support the development of novel clinical therapies.

Prolonged intracellular accumulation of light-inducible nanoparticles in leukemia cells allows their remote activation.

Leukaemia cells that are resistant to conventional therapies are thought to reside in protective niches. Here, we describe light-inducible polymeric retinoic acid (RA)-containing nanoparticles (NPs) with the capacity to accumulate in the cytoplasm of leukaemia cells for several days and release their RA payloads within a few minutes upon exposure to blue/UV light. Compared to NPs that are not activated by light exposure, these NPs more efficiently reduce the clonogenicity of bone marrow cancer cells from patients with acute myeloid leukaemia (AML) and induce the differentiation of RA-low sensitive leukaemia cells. Importantly, we show that leukaemia cells transfected with light-inducible NPs containing RA can engraft into bone marrow in vivo in the proximity of other leukaemic cells, differentiate upon exposure to blue light and release paracrine factors that modulate nearby cells. The NPs described here offer a promising strategy for controlling distant cell populations and remotely modulating leukaemic niches.

Nanomedicine Approaches to Modulate Neural Stem Cells in Brain Repair.

We explore the concept of modulating neural stem cells and their niches for brain repair using nanotechnology-based approaches. These approaches include stimulating cell proliferation, recruitment, and differentiation to functionally recover damaged areas. Nanoscale-engineered materials potentially overcome limited crossing of the blood-brain barrier, deficient drug delivery, and cell targeting.