ATR Inhibition Broadly Sensitizes Soft-Tissue Sarcoma Cells to Chemotherapy Independent of Alternative Lengthening Telomere (ALT) Status.

Only few drugs have shown activity in patients with advanced soft-tissue and the median overall survival is only 18 months. Alterations of genes involved in the DNA damage repair pathway have been associated with sarcoma risk and prognosis. ATR plays a crucial role in maintaining genomic integrity by responding to a large spectrum of DNA damage, including double strand breaks (DSBs) that interfere with replication.

Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential of Polyps.

Objective: Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free.

Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.

There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs.

High-throughput production of optimized primers (fimers) for whole-genome direct sequencing.

Fimers are specifically modified primers selected to inhibit nonspecific interactions occurring in cycle sequencing. They are postsynthetically derived from 2'-methoxyoxalamido or 2'-succinimido precursor oligonucleotides by treatment with appropriate small molecular weight modifiers (a primary aliphatic amine or hydroxide anion). We describe design, synthesis, and purification of fimers, and their use in protocols for direct sequencing of genomic deoxyribonucleic acid (DNA).

The complete genome of hyperthermophile Methanopyrus kandleri AV19 and monophyly of archaeal methanogens.

We have determined the complete 1,694,969-nt sequence of the GC-rich genome of Methanopyrus kandleri by using a whole direct genome sequencing approach. This approach is based on unlinking of genomic DNA with the ThermoFidelase version of M. kandleri topoisomerase V and cycle sequencing directed by 2'-modified oligonucleotides (Fimers).