Decentralization of Next-Generation RNA Sequencing-Based MammaPrint® and BluePrint® Kit at University Hospitals Leuven and Curie Institute Paris.

A previously developed and centrally validated MammaPrint® (MP) and BluePrint® (BP) targeted RNA next-generation sequencing (NGS) kit was implemented and validated in two large academic European hospitals. Additionally, breast cancer molecular subtypes by MP and BP RNA sequencing were compared with immunohistochemistry (IHC). Patients with early breast cancer diagnosed at University Hospitals Leuven and Curie Institute Paris were prospectively included between September 2017 and January 2018.

Identification of miRNA modulators to PARP inhibitor response.

Based on the principle of synthetic lethality, PARP inhibitors have been shown to be very effective in killing cells deficient in homologous recombination (HR), such as those bearing mutations in BRCA1/2. However, questions regarding their wider use persist and other determinants of responsiveness to PARP inhibitor remain to be fully explored. MicroRNAs (miRNAs) are small non-coding RNAs, which serve as post-transcriptional regulators of gene expression and are involved in a wide variety of cellular processes, including the DNA damage response (DDR).

Targeted radiosensitization by the Chk1 inhibitor SAR-020106.

Purpose: To explore the activity of a potent Chk1 inhibitor (SAR-020106) in combination with radiation.

Methods And Materials: Colony and mechanistic in vitro assays and a xenograft in vivo model.

Results: SAR-020106 suppressed-radiation-induced G2/M arrest and reduced clonogenic survival only in p53-deficient tumor cells.

Targeted radiosensitization of cells expressing truncated DNA polymerase {beta}.

Ionizing radiation (IR) is an effective anticancer treatment, although failures still occur. To improve radiotherapy, tumor-targeted strategies are needed to increase radiosensitivity of tumor cells, without influencing normal tissue radiosensitivity. Base excision repair (BER) and single-strand break repair (SSBR) contribute to the determination of sensitivity to IR.

Mechanism of cell killing after ionizing radiation by a dominant negative DNA polymerase beta.

Several types of DNA lesion are induced after ionizing irradiation (IR) of which double strand breaks (DSBs) are expected to be the most lethal, although single strand breaks (SSBs) and DNA base damages are quantitatively in the majority. Proteins of the base excision repair (BER) pathway repair these numerous lesions. DNA polymerase beta has been identified as a crucial enzyme in BER and SSB repair (SSBR).

Radiosensitization by a dominant negative to DNA polymerase beta is DNA polymerase beta-independent and XRCC1-dependent.

Background And Purpose: DNA base damages and single strand breaks after ionizing radiation are repaired by base excision repair (BER) and single strand break repair (SSBR), with both DNA polymerase beta (polbeta) and XRCC1 playing key roles. We previously showed that a dominant negative to polbeta (polbetaDN) sensitized human tumor cells to ionizing radiation. However, polbeta-deficient cells, in contrast to XRCC1-deficient cells, are not more radiosensitive.

Quantitative reverse transcription-polymerase chain reaction measurement of HASH1 (ASCL1), a marker for small cell lung carcinomas with neuroendocrine features.

Purpose: The Human Achaete-Scute homologue 1 (HASH1, ASCL1), a lineage-specific basic helix-loop-helix member of the achaete-scute family, is essential for the generation of pulmonary neuroendocrine (NE) cells during lung development. In small cell lung cancer (SCLC), the most lethal form of lung cancer, the gene is highly expressed and the expression of HASH1 correlates with NE features found in SCLCs. Here we describe a highly sensitive reverse transcription-PCR method for quantifying HASH1 mRNA in clinical samples, using real-time fluorescence resonance energy transfer technology (LightCycler).