Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2’-deoxyuridine. Erythrocy...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder of nucleoside metabolism that is caused by mutations in the nuclear thymidine phosphorylase gene (TYMP) gene, encoding for the enzyme thymidin...
Tagging proliferating cells with thymidine analogs is an indispensable research tool; however, the issue of the potential in vivo cytotoxicity of these compounds remains unresolved. Here, we address these concerns by examining the effects of BrdU and...
Polyamine spermidine is essential for the proliferation of eukaryotic cells. Administration of polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO) induces cytostasis that occurs in two phases; the early phase which can be reversed by sp...
Tritiated thymidine autoradiography, 5-bromo-2′-deoxyuridine (BrdU) 5-chloro-2′-deoxyuridine (CldU), 5-iodo-2′-deoxyuridine (IdU), and 5-ethynyl-2′-deoxyiridine (EdU) labeling have been used for identifying the fraction of cel...
Two kinds of novel thymidine derivatives, N-thymidine-yl-N′-methyl-N′-{N′′-[2-sulfanyl-(ethylamino)acetyl]-2-aminoethylsulfanyl-1-hexanamide}-ethanediamine (TMHEA) and N-thymidine-yl-N′-methyl-N′-{N′′-[2-sulfanyl-(ethylamino)acetyl]-2-aminoethylsulfa...
Gene-directed enzyme prodrug therapy (GDEPT) has been developed over several decades as a targeted cancer treatment aimed at minimizing toxicity to healthy cells. This approach involves three key components: a non-toxic prodrug, a gene encoding an en...
Human induced pluripotent stem cells (iPSCs) hold enormous promise for regenerative medicine. The major safety concern is the tumorigenicity of transplanted cells derived from iPSCs. A potential solution would be to introduce a suicide gene into iPSC...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder which primarily affects the gastrointestinal and nervous systems. This disease is caused by mutations in the nuclear TYMP gene, which encodes for thymidi...
Achieving a 99mTc labeled thymidine radiotracer for single photon emission tomography (SPECT) is considered to be of interest. In this study, four novel thymidine analogs, 6a, 6b, 6c and 6d, were successfully synthesized via “click reaction” route an...
We have synthesized quinoxaline analogs (1–25), characterized by 1H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxan...
Oncolytic viruses are a promising class of anti-tumor agents; however, concerns regarding uncontrolled viral replication have led to the development of a replication-controllable oncolytic vaccinia virus (OVV). The engineering involves replacing the...
Thymidine kinase 1 (TK1) phosphorylates thymidine nucleosides to generate thymidine monophosphate. This reaction belongs to the pyrimidine salvage route that is phylogenetically conserved. In the model plant Arabidopsis thaliana, TK activity contribu...
Overexpression of the thymidine phosphorylase (TP) enzyme induces angiogenesis, which eventually leads to metastasis and tumor growth. The crucial role of TP in cancer development makes it an important target for anticancer drug discovery. Currently,...
Pseudorabies (also called Aujeszky’s disease) is a highly infectious viral disease caused by the pseudorabies virus (PRV, or Suid herpesvirus 1). Although the disease has been controlled by immunization with the PRV-attenuated vaccine, the emer...
Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity and is frequently diagnosed at an advanced stage, resulting in poor prognosis and limited treatment options. Identifying reliable biomarker...
Breast cancer (BC) is the most frequent non-cutaneous malignancy in women. Histological grade, expression of estrogen and progesterone receptors (ER and PgR), overexpression/amplification of the human epidermal growth factor receptor 2 (HER2) oncogen...
The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV) system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly r...
Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival...
After heart disease, cancer is the second-leading cause of death worldwide. The most effective method of cancer treatment is target therapy. One of the potential goals of therapy could be DT-diaphorase, which reduces quinone moiety to hydroquinone, a...
Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a bi...
Marek’s disease (MD) is a ubiquitous disease of domesticated chickens and its etiologic agent is the Gallid alphaherpesvirus 2 (GaHV-2), also known as Marek’s disease virus (MDV). MD is currently controlled by vaccination using live atten...
The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alky...
Viral replication of thymidine kinase deleted (tk−) vaccinia virus (VV) is attenuated in resting normal cells, enabling cancer selectivity, however, replication potency of VV-tk− appears to be diminished in cancer cells. Previously, we fo...
Pathologic complete response (pCR) predicts the long-term outcome of neoadjuvantly treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers enabling adjustment or interruption of an ineffective ther...
Tapping panel dryness (TPD) syndrome is one of the latex yield affecting factors in the rubber tree (Hevea brasiliensis Mull. Arg.). Therefore, identification of a DNA marker will be highly useful for screening progenies in breeding programs. The maj...
Inflammation and fibrosis in human liver are often precursors to hepatocellular carcinoma (HCC), yet none of them is easily modeled in animals. We previously generated transgenic mice with hepatocyte-specific expressed herpes simplex virus thymidine...
Objectives: Few studies have explored the use of spectral dual-layer detector-based computed tomography (SDCT) parameters, thymidine kinase-1 (TK1), and tumor abnormal protein (TAP) for the detection of ground-glass nodules (GGNs). Therefore, we aime...
Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation...
Immune checkpoint inhibitors (ICIs) are widely used in cancer immunotherapy, requiring effective methods for response monitoring. This study evaluated changes in 18F-2-fluoro-2-deoxy-D-glucose (FDG) and 18F-fluorothymidine (FLT) uptake by tumors foll...
Serological thymidine kinase 1 (STK1) is a reliable proliferation marker for prognosis, monitoring tumour therapy, and relapse. Here we investigated the use of STK1 in health screening for early detection of pre-malignant and malignant diseases. The...
An important disadvantage of plastics is their fragmentation into smaller particles, classified according to size as microplastics and nanoplastics. These plastic particles persist for extended periods in aerial, terrestrial, and aquatic ecosystems a...
One of the most essential health problems is cancer, the first or second cause of death worldwide. Head and neck cancers are hard to detect due to non-specific symptoms. The treatment often relies on a combination of radio and chemotherapy. For this...
Cell therapies based on pluripotent stem cells (PSC), have opened new therapeutic strategies for neurodegenerative diseases. However, insufficiently differentiated PSC can lead to tumor formation. Ideally, safety switch therapies should selectively k...
Background/Objectives: Nucleoside precursors and derivatives play pivotal roles in the development of antimicrobial and antiviral therapeutics. The 2022 global outbreak of monkeypox (Mpox) across more than 100 nonendemic countries underscores the urg...
Nucleoside analogues (NA) are prodrugs that are phosphorylated by deoxyribonucleoside kinases (dNKs) as the first step towards a compound toxic to the cell. During the last 20 years, research around dNKs has gone into new organisms other than mammals...
G-quadruplex (G4) DNA structures have recently emerged as promising chiral scaffolds for enantioselective catalysis. This study investigates how thymidine loop modifications influence the catalytic performance of the telomeric G4 sequence HT21 in the...
Modification of synthetic oligonucleotides and DNA is widely used in many applications in the life sciences. However, in most cases, modified DNA cannot be restored to its native state. Here, we report the preparation of a thymidine-inosine dimer bui...
Lipase from Candida rugosa (CRL) was stabilized at alkaline pH to overcome the inactivation problem and was immobilized for the first time by multipoint covalent attachment on different aldehyde-activated matrices. PEG was used as a stabilizing agent...
In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and...
The effectiveness of acyclovir, a selective anti-herpesvirus agent, was tested both in silico and in vitro against two ranaviruses, namely the European catfish virus (ECV) and Frog virus 3 (FV3). ECV can cause significant losses in catfish aquacultur...
Gapmer-type antisense oligonucleotides (ASOs) are an emerging class of therapeutic agents that directly inhibit pathogenic mRNA. In this study, three new 4′-C-substituted thymidine analogs were generated using a synthetic strategy recently esta...
Mesenchymal stem/stromal cells (MSCs) prepared from various human tissues were stably transduced with the suicide gene herpes simplex virus thymidine kinase (HSVTK) by means of retrovirus infection. HSVTK-transduced MSCs express the suicide gene and...
Loss of the transcription factor p53 implies mRNA losses of target genes such as the p53R2 subunit of human ribonucleotide reductase (RNR). We hypothesized that other genes in the dNTP supply system would compensate for such p53R2 losses and looked f...
Oligonucleotide conjugates are versatile scaffolds that can be applied in DNA-based screening platforms and ligand display or as therapeutics. Several different chemical approaches are available for functionalizing oligonucleotides, which are often c...
Curcumin is a dietary compound with accrued evidence of antiviral activity. Poor solubility and permeation renders curcumin a good applicant for incorporation into proniosomes. The intent of this study was to formulate curcumin proniosomal gel for to...
The thymidine kinase (TK) and DNA polymerase (pol) genes of the herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are two important genes involved in antiviral resistance. We investigated the genetic polymorphisms of the HSV-TK and pol genes i...
The bicyclic nucleoside analogue (BCNA) Cf1743 and its orally bioavailable prodrug FV-100 have unique potential as varicella-zoster virus (VZV) inhibitors to treat herpes zoster (shingles) and the therewith associated pain, including post-herpetic ne...
With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression by means of positron emission tomography (PET), a novel [18F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(h...
28 April 2010
Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-...
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