Whole-Person Learning: Lessons from Integral Health-Care Practitioners and Their Implications for Adult Education

For over a decade, I’ve studied the humanities, education and Complementary and Alternative Medicine. It began as a personal interest and transformed into a professional one. As an undergraduate psychology student, I explored the mind and the various methods of psychotherapy. During graduate school, I became exposed to eastern philosophies and religions, and I began practicing meditation as a means to quiet the mind and bring my life into balance. As I followed this path, it led to several trainings in holistic studies including a massage therapy program, a yoga teacher training and a certification in Healing Touch, an energy-based approach to health and healing

Current Strategies for Identification of Glioma Stem Cells: Adequate or Unsatisfactory?

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments. Markers for glioblastoma stem cells such as CD133, CD15, integrin-α6, L1CAM might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead to carefully consider the techniques employed so far to isolate these cells. Due to a dearth of methods and markers reliably identifying the candidate cancer stem cells, the isolation/enrichment of cancer stem cells to be therapeutically targeted remains a major challenge

Genomics of Acute Myeloid Leukemia: The Next Generation

Acute myeloid leukemia (AML) is, as other types of cancer, a genetic disorder of somatic cells. The detection of somatic molecular abnormalities that may cause and maintain AML is crucial for patient stratification. The development of mutation-specific therapeutic interventions will hopefully increase cure rates and improve patients’ quality of life. This review illustrates how next generation sequencing technologies are changing the study of cancer genomics of adult AML patients

Arsenic trioxide (ATO) and MEK1 inhibition synergize to induce apoptosis in acute promyelocytic leukemia cells

Recent studies suggest that components of the prosurvival signal transduction pathways involving the Ras-mitogen-activated protein kinase ( MAPK) can confer an aggressive, apoptosis-resistant phenotype to leukemia cells. In this study, we report that acute promyelocytic leukemia (APL) cells exploit the Ras-MAPK activation pathway to phosphorylate at Ser112 and to inactivate the proapoptotic protein Bad, delaying arsenic trioxide (ATO)-induced apoptosis. Both in APL cell line NB4 and in APL primary blasts, the inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) and Bad phosphorylation by MEK1 inhibitors enhanced apoptosis in ATO-treated cells. We isolated an arsenic-resistant NB4 subline (NB4-As-R), which showed stronger ERK1/2 activity (2.7-fold increase) and Bad phosphorylation (2.4-fold increase) compared to parental NB4 cells in response to ATO treatment. Upon ATO exposure, both NB4 and NB4-As-R cell lines doubled protein levels of the death antagonist Bcl-xL, but the amount of free Bcl-xL that did not heterodimerize with Bad was 1.8-fold greater in NB4-As-R than in the parental line. MEK1 inhibitors dephosphorylated Bad and inhibited the ATO-induced increase of Bcl-xL, overcoming ATO resistance in NB4-As-R. These results may provide a rationale to develop combined or sequential MEK1 inhibitors plus ATO therapy in this clinical setting

Nanoscale Distribution of Nuclear Sites by Super-Resolved Image Cross-Correlation Spectroscopy

Deciphering the spatiotemporal coordination between nuclear functions is important to understand its role in the maintenance of human genome. In this context, super-resolution microscopy has gained considerable interest because it can be used to probe the spatial organization of functional sites in intact single-cell nuclei in the 20\u2013250 nm range. Among the methods that quantify colocalization from multicolor images, image cross-correlation spectroscopy (ICCS) offers several advantages, namely it does not require a presegmentation of the image into objects and can be used to detect dynamic interactions. However, the combination of ICCS with super-resolution microscopy has not been explored yet. Here, we combine dual-color stimulated emission depletion (STED) nanoscopy with ICCS (STED-ICCS) to quantify the nanoscale distribution of functional nuclear sites. We show that super-resolved ICCS provides not only a value of the colocalized fraction but also the characteristic distances associated to correlated nuclear sites. As a validation, we quantify the nanoscale spatial distribution of three different pairs of functional nuclear sites in MCF10A cells. As expected, transcription foci and a transcriptionally repressive histone marker (H3K9me3) are not correlated. Conversely, nascent DNA replication foci and the proliferating cell nuclear antigen(PCNA) protein have a high level of proximity and are correlated at a nanometer distance scale that is close to the limit of our experimental approach. Finally, transcription foci are found at a distance of 130 nm from replication foci, indicating a spatial segregation at the nanoscale. Overall, our data demonstrate that STED-ICCS can be a powerful tool for the analysis of the nanoscale distribution of functional sites in the nucleus

CARPET: a web-based package for the analysis of ChIP-chip and expression tiling data

Summary: CARPET (Collection of Automated Routine Programs for Easy Tiling) is a set of Perl, Python and R scripts, integrated on the Galaxy2 web-based platform, for the analysis of ChIP-chip and expression tiling data, both for standard and custom chip designs. CARPET allows rapid experimental data entry, simple quality control, normalization, easy identification and annotation of enriched ChIP-chip regions, detection of the absolute or relative transcriptional status of genes assessed by expression tiling experiments and, more importantly, it allows the integration of ChIP-chip and expression data. Results can be visualized instantly in a genomic context within the UCSC genome browser as graph-based custom tracks through Galaxy2. All generated and uploaded data can be stored within sessions and are easily shared with other users. Availability: http://bio.ifom-ieo-campus.it/galaxy Contacts: [email protected] lucilla.luzi@if om-ieo-campus.i

Secondary mechanisms of anti-HER2 resistance in breast cancer: NF1 as an actionable target

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Is PML a tumor suppressor?

The role of the promyelocytic leukemia (PML) protein has been widely tested in many different contexts, as attested by the hundreds of papers present in the literature. In most of these studies, PML is regarded as a tumor suppressor, a notion on the whole accepted by the scientific community. In this review, we examine how the concept of tumor-suppressor gene has evolved until now and then systematically assess whether this assumption for PML is supported by unambiguous experimental evidence