The Controversial Clinicobiological Role of Breast Cancer Stem Cells

Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. Growing experimental evidence suggests that cancer stem cells (CSCs) may contribute to tumor progression and metastasis spread. However, despite the tremendous clinical potential of such cells and their possible therapeutic management, the real nature of CSCs remains to be elucidated. Starting from what is currently known about normal mammary stem/progenitor cells, to better define the cell that originates a tumor or is responsible for metastatic spread, this review will discuss experimental evidence of breast cancer stem cells and speculate about the clinical importance and implications of their evaluation

MODELLO SPERIMENTALE DI FLOGOSI INDOTTA DAL COMPESSO TERMINALE DEL COMPLEMENTO NEL SISTEMA NERVOSO CENTRALE DI RATTO

1999/2000XII Ciclo1965Versione digitalizzata della tesi di dottorato cartacea

Pharmacological Effects of the Ruthenium Complex NAMI-A Given Orally to CBA Mice With MCa Mammary Carcinoma

NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, is a ruthenium based compounds capable of inhibiting the growth of lung metastases of solid tumours in a number of experimental conditions.The aim of this study was to investigate the potential use of NAMI-A by the oral route to treat lung metastases of MCa mammary carcinoma in the CBA mouse. treatment of mice, carrying intramuscular tumours in advanced stage of growth, for 11 consecutive days caused a significant reduction of the weight of lung metastases over the range of doses from 150 to 600 mg/kg/day. No sign of toxicity was observed at the histological analysis in the gut epithelium or in the kidney parenchyma, and NAMI-A concentration in the kidney was more than 10-fold lower than after intraperitoneal treatments. NAMI-A is thus active against metastases also by the oral route, suggesting the use of this way to treat tumour bearing hosts for long periods

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via Angiotensin Type 1 receptor: evidence from brain regional sensitivity to amphetamine

Amphetamine‐induced neuroadaptations involve vascular damage, neuroinflammation, a hypo‐functioning prefrontal cortex (PFC) as well as cognitive alterations. Brain angiotensin II, through Angiotensin Type 1 receptor (AT1‐R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT1‐R in the development of amphetamine‐induced changes over glial and vascular components within PFC and hippocampus. Attention deficit was evaluated as a behavioral neuroadaptation induced by amphetamine. Brain microvessels were isolated to further evaluate vascular alterations after amphetamine exposure. Male Wistar rats were administered with AT1‐R antagonist, Candesartan, followed by repeated amphetamine. After one week drug‐off period, animals received a saline or amphetamine challenge and were evaluated in behavioral tests. Afterwards, their brains were processed for cresyl violet staining, CD11b (microglia marker), GFAP (astrocyte marker) or von Willebrand factor (vascular marker) immunohistochemistry, and oxidative/cellular stress determinations in brain microvessels. Statistical analysis was performed by using Factorial ANOVA followed by Bonferroni or Tukey tests. Repeated amphetamine administration increased astroglial and microglial markers immunoreactivity, increased apoptotic cells and promoted vascular network rearrangement at the PFC concomitantly with an attention deficit. Although, the amphetamine challenge improved the attentional performance, it triggers detrimental effects probably because of the exacerbated malondialdehyde levels and increased heat shock protein 70 expression in microvessels. All observed amphetamine‐induced alterations were prevented by the AT1‐R blockade. Our results support the AT1‐R involvement in the development of oxidative/inflammatory conditions triggered by amphetamine exposure, affecting cortical areas and increasing vascular susceptibility to future challenges.Fil: Marchese, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Casarsa, Brenda Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Baiardi, Gustavo Carlos. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin

Angiotensin II AT 1 Receptors Stimulation

Central nucleus of the amygdala (CeA) is one of the most important regulatory centres for the emotional processes. Among the different neurotransmitter systems present in this nucleus, AT 1 receptors have been also found, but their role in the generation and modulation of emotions is not fully understood. The present work evaluated the effect of intra-amygdalar injection of losartan (AT 1 receptor antagonist) and angiotensin II (Ang II) in the anxiety state induced by fear-potentiated plus maze in male Wistar rats. Fear in the elevated plus maze can be potentiated by prior inescapable footshock stress. The decrease in the time spent in the open arms induced by the inescapable footshock was totally prevented by losartan (4 pmol) administration in CeA. It was also found that Ang II (48 fmol) administration decreased the time spent in the open arms in animals with or without previous footshock exposure. The locomotor activity and grooming behaviour were also evaluated. The results obtained from the different parameters analyzed allowed us to conclude that the Ang II AT 1 receptors in CeA are involved in the anxiety state induced by stress in the fear-potentiated plus-maze behaviour

The interaction of asbestos fibres with human mesothelial cells: a combined investigation exploiting microscopic and nanoscopic techniques

Introduction. The exposure to asbestos fibres is associated with the development of severe diseases such as lung cancer and pleural mesothelioma. The interaction mechanism of these fibres with the mesothelial cells is still debated.(1) This work aims at obtaining information about the interaction of crocidolite fibres with mesothelial cells, for a better understanding of the processes that trigger cell transformation. For this reason we combine optical microscopy and SEM, with nanoscopic techniques as near-field optical (SNOM) and atomic force microscopy (AFM). These two latter techniques, thanks to their high sensitivity and non-invasiveness, are suitable for investigating phenomena occurring at the cell membrane with nanometric resolution.(2) In addition, SNOM provides simultaneous topography and optical image with a resolution beyond the light diffraction limit. This allows a direct coupling of the morphological features with the optical properties of the sample. Materials and Methods. Mesothelial cell line (MET5A from ATCC) are grown in RPMI with FCS 10%, 2 mM glutamine. Cells are exposed to 5µg/cm2 crocidolite for 3, 6 or 12 h. For optical microscopy cells are stained with Diff-Quick. The samples after fixation with PFA 4% are prepared for SEM, SNOM and AFM observations that are carried out by using a Leica Stereoscan 430i, a A-100 AFM and TriA-SNOM microscope (A.P.E.Research, Trieste, Italy). Results and Discussion. By analysing the optical data we estimate that fibres are associated with 75% of mesothelial cells. SEM images confirm these results and allow distinguishing that some fibres are on cell surface, while others appears to be clearly inside the cells, in some cases even deforming the cell morphology. A deeper investigation is achieved by SNOM and AFM. By comparing the SNOM topography with the simultaneous transmission and reflection images, we can define the position of the fibres respect to the cell membrane, owing to difference in optical properties between the crocidolite and the cell material. In addition, high-resolution AFM images highlight the entrance site of the nanometre-size fibres at cell membrane. In conclusion the combination of our findings provides an accurate description about the interaction of mesothelial cells with crocidolite fibres having different size. Importantly, SNOM optical images can disclose details about such interaction not observed up to now. 1. Arch. Biochem. Biophys. 2010, 502: 1. 2. J. Cell Sci. 2001, 114: 4153

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

Towards a Muon Collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.Comment: 118 pages, 103 figure

Erratum:Towards a muon collider

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