PopulationProfiler: A Tool for Population Analysis and Visualization of Image-Based Cell Screening Data.

Image-based screening typically produces quantitative measurements of cell appearance. Large-scale screens involving tens of thousands of images, each containing hundreds of cells described by hundreds of measurements, result in overwhelming amounts of data. Reducing per-cell measurements to the averages across the image(s) for each treatment leads to loss of potentially valuable information on population variability.

Targeting DNA repair, DNA metabolism and replication stress as anti-cancer strategies.

Anti-cancer therapies targeting and damaging the DNA have been extensively used in the last 50 years since the discovery of nitrogen mustards, antimetabolites and platin agents. The use of these drugs is often limited by dose-limiting side effects related to their poor specificity. In recent years, much effort has been put on the discovery and development of compounds that would exploit defects in DNA repair in cancer cells such as Wee1, Chk1 or PARP1 inhibitors.

Processing of protein ADP-ribosylation by Nudix hydrolases.

ADP-ribosylation is a post-translational modification (PTM) of proteins found in organisms from all kingdoms of life which regulates many important biological functions including DNA repair, chromatin structure, unfolded protein response and apoptosis. Several cellular enzymes, such as macrodomain containing proteins PARG [poly(ADP-ribose) glycohydrolase] and TARG1 [terminal ADP-ribose (ADPr) protein glycohydrolase], reverse protein ADP-ribosylation. In the present study, we show that human Nudix (nucleoside diphosphate-linked moiety X)-type motif 16 (hNUDT16) represents a new enzyme class that can process protein ADP-ribosylation in vitro, converting it into ribose-5'-phosphate (R5P) tags covalently attached to the modified proteins.

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death.

Combining doublecortin-like kinase silencing and vinca alkaloids results in a synergistic apoptotic effect in neuroblastoma cells.

Microtubule-destabilizing agents, such as vinca alkaloids (VAs), are part of the treatment currently applied in patients with high-risk neuroblastoma (NB). However, the development of drug resistance and toxicity make NB difficult to treat with these drugs. In this study we explore the combination of VAs (vincristine or vinblastine) with knockdown of the microtubule-associated proteins encoded by the doublecortin-like kinase (DCLK) gene by using short interference RNA (siRNA).

Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells.

Cellular responses to DNA-damaging agents involve the activation of various DNA damage signaling and transduction pathways. Using quantitative and high-resolution tandem mass spectrometry, we determined global changes in protein level and phosphorylation site profiles following treatment of SILAC (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected.

Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

Unlabelled: Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α).

High-throughput live cell imaging of apoptosis.

Apoptosis is important for embryonic development, tissue homeostasis, and removal of cells with (potentially transforming) DNA lesions or other types of injuries. Functional genomics screens performed to unravel apoptotic signaling cascades in the context of toxicant-induced cell injury commonly use apoptosis as an end-point. Here, a method to detect the accumulation of apoptotic cells in real time that is well suited for high-throughput screens is described.

Silencing of the microtubule-associated proteins doublecortin-like and doublecortin-like kinase-long induces apoptosis in neuroblastoma cells.

Doublecortin-like kinase-long (DCLK-long) and doublecortin-like (DCL) are two splice variants of DCLK gene. DCL and DCLK-long are microtubule-associated proteins with specific expression in proliferative neural progenitor cells. We have tested the hypothesis that knockdown of DCL/DCLK-long by RNA interference technology will induce cell death in neuroblastoma (NB) cells.

The cancer stem cell microenvironment and anti-cancer therapy.

Purpose: Tumours are composed of a heterogeneous cell population. Cancer stem cells, which make up a minor fraction of a tumour, may be the cells that initiate and sustain tumour growth. Cancer stem cells are believed to share many properties with normal stem cells that render them relatively insensitive to classical radio- and chemotherapy.

Cross-talk between integrins and oncogenes modulates chemosensitivity.

Chemotherapy often relies on cancer cell death resulting from DNA damage. The p53 tumor suppressor pathway that is an important player in DNA damage response is frequently inactivated in cancer. Genotoxicants also activate DNA damage-independent stress pathways and activity of oncogenic signaling and adhesive interactions with the cancer microenvironment can have a strong impact on chemosensitivity.

Dental health differences by social class in home-dwelling seniors of Barcelona, Spain.

Background: The aim of this study was to assess dental health differences by social class in home-dwelling seniors in Spain.

Methods: A cross-sectional household survey of a cohort of senior residents in Barcelona (Spain) was undertaken. Of 891 survivors (72 years or older), 561 (62.