Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2'-deoxyuridine (EdU) and 5-Chloro-2'-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2'-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923809 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088629 | PLOS |
Sci Rep
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary.
Hydrogen sulfide (HS) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-HS-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Department of Surgery, Japan Community Healthcare Organization Tokuyama Central Hospital, 1-1 Koda-Cho, Shunan, Yamaguchi, 745-0822, Japan.
Purpose: We aimed to identify the risk factors for severe neutropenia in the early phase of trifluridine-tipiracil (FTD/TPI) treatment, and their impact on overall survival (OS).
Methods: This single-center retrospective study included patients with unresectable metastatic colorectal cancer who were treated with FTD/TPI. The primary endpoint was OS, and the secondary endpoint was severe neutropenia during the first and second cycles of FTD/TPI.
Viruses
December 2024
HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL.
View Article and Find Full Text PDFESMO Open
January 2025
Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan; Department of Comprehensive Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:
Background: Pembrolizumab, an immune checkpoint inhibitor (ICI), shows significant survival benefits in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but its efficacy in microsatellite-stable (MSS) mCRC is limited. Although ICIs are effective in tumor mutational burden-high (TMB-H) solid tumors, the impact on MSS-TMB-H mCRC, a rare subset within MSS mCRC, remains unclear.
Materials And Methods: We conducted a retrospective analysis using clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository in Japan.
Front Immunol
January 2025
Laboratory of Fish Protistology, Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice, Czechia.
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