Liquid Biopsy in Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer deaths worldwide. To date, the gold standard for the molecular analysis of a patient affected by NSCLC is the tissue biopsy. The discovery of activating mutations and rearrangements in specific genes has revolutionized the therapeutic approaches of lung cancer over the last years. For this reason, a strict \u201cmolecular follow-up\u201d is mandatory to evaluate patient\u2019s disease evolution. Indeed, liquid biopsy has raised as the \u201cnew ambrosia of researchers\u201d as it could help clinicians to identify both prognostic and predictive biomarkers in a more accessible way. Liquid biopsy analysis can be used in different moments starting from diagnosis to relapse, earning multiple clinical meanings, offering thus a noninvasive but valid method to detect actionable mutations. Although the implementation of both exosomes and CTCs in clinical practice is several steps back, new advances and discoveries make them, together with the ctDNA, a very promising tool. In the following chapter we will discuss the recent advances of liquid biopsy in NSCLC highlighting the possible clinical utility of CTCs, ctDNA and exosomes

Systems-Level Modeling of Cancer-Fibroblast Interaction

Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchymal cells, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may prove useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts

Vacation (after-) effects on employee health and well-being, and the role of vacation activities, experiences and sleep

Contains fulltext : 116760.pdf (publisher's version ) (Open Access)Most vacations seem to have strong, but rather short-lived effects on health and well-being (H&W). However, the recovery-potential of relatively long vacations and the underlying processes have been disregarded. Therefore, our study focused on vacations longer than 14 days and on the psychological processes associated with such a long respite from work. In the present study, we investigated (1) how health and well-being (H&W) develop during and after a long summer vacation, (2) whether changes in H&W during and after vacation relate to vacation activities and experiences and (3) whether changes in H&W during and after vacation relate to sleep. Fifty-four employees reported their H&W before, three or four times during and five times after vacation. Vacations lasted 23 days on average. Information on vacation experiences, work-related activities and sleep was collected during vacation. Vacation activities were assessed immediately after vacation. H&W increased quickly during vacation, peaked on the eighth vacation day and had rapidly returned to baseline level within the first week of work resumption. Vacation duration and most vacation activities were only weakly associated with H&W changes during and after vacation. Engagement in passive activities, savoring, pleasure derived from activities, relaxation, control and sleep showed strong relations with improved H&W during and to a lesser degree after vacation. In conclusion, H&W improved during long summer vacations, but this positive effect was short-lived. Vacation experiences, especially pleasure, relaxation, savoring and control, seem to be especially important for the strength and persistence of vacation (after-) effects

Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay

This work describes the coupling of the IR-MALDESI imaging source with the Q Exactive mass spectrometer. IR-MALDESI MSI was used to elucidate the spatial distribution of several HIV drugs in cervical tissues that had been incubated in either a low or high concentration. Serial sections to those analyzed by IR-MALDESI MSI were homogenized and analyzed by LC-MS/MS to quantify the amount of each drug present in the tissue. By comparing the two techniques, an agreement between the average intensities from the imaging experiment with the absolute quantities for each drug was observed. This correlation between these two techniques serves as a prerequisite to quantitative IR-MALDESI MSI. In addition, a targeted MS(2) imaging experiment was also conducted to demonstrate the capabilities of the Q Exactive and to highlight the added selectivity that can be obtained with SRM or MRM imaging experiments

Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo

A class of drugs, called kinase inhibitors, could stop cancer in its tracks…if only these drugs could reach the tumors, stay for a while, and not be toxic. Hypothesizing that a nanoparticle formulation would solve the inhibitors’ woes, Ashton and colleagues investigated several different compositions of so-called Accurins—polymeric particles that encapsulate charged drugs through ion pairing. An Aurora B kinase, once formulated in Accurins, demonstrated a much-improved therapeutic index and preclinical efficacy compared with its parent molecule, when administered to rats and mice bearing human tumors. The Accurins allowed for sustained release of the drug over days, and did not have the same blood toxicity seen with the parent drug. A phase 1 trial is the next step for this nanomedicine, and additional preclinical studies will reveal whether such nanoformulations can improve the tolerability and efficacy of the broader class of molecularly targeted cancer therapeutics, including cell cycle inhibitors