Herpes simplex virus type 1, strain Kupka, did not replicate in chick embryo fibroblasts (CEF), but the infection was followed by the development of cytopathic changes. This effect could be abolished by UV irradiation of the virus. Virus-induced thymidine kinase was synthesized in the infected cells reaching a maximum level at 24 hours post infection (p.i.). In the presence of cytosine arabinoside, thymidine kinase synthesis was enhanced. This suggested that the late (post-replicative) viral function, which turns off thymidine kinase synthesis, was expressed in the infected CEF untreated with the drug. HSV type 1 laboratory strains Kupka and KOS were capable of inducing the synthesis of virus-specific DNA in CEF. But in CEF infected with fresh type 1 virus isolates replication of viral DNA was not observed.
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Cancer Res Commun
January 2025
Candel Therapeutics, Needham, MA, United States.
CAN-2409 is a replication-defective adenovirus that delivers the herpes simplex virus (HSV)-thymidine kinase gene to infected cells. Intratumoral administration of CAN-2409 followed by prodrug results in the formation of a toxic metabolite able to induce immunogenic cell death, exposure of tumor-associated antigens, and activation of local and systemic immune responses. We used a dynamic labeling model with MC38 tumor cells implanted in photoconvertible Kaede mice.
View Article and Find Full Text PDFWorld J Oncol
February 2025
The First Clinical Medical School, Jinan University, Guangzhou 510632, Guangdong, China.
Background: Thymidine kinases (TKs) are key enzymes involved in DNA synthesis and repair, with alterations in their expression associated with various cancers. Thymidine kinase 1 (TK1) and TK2 are cytosolic enzyme proteins that catalyze the addition of a gamma-phosphate group to thymidine. The existing literature on TK1 in cervical squamous cell carcinoma (CESC) fails to address the clinical role of TK1 overexpression and its possible molecular mechanism in CESC.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
View Article and Find Full Text PDFAnn Med
December 2025
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Background: We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, and found significant differences in pyrimidine metabolites. The PMGs is associated with the clinical prognosis of several cancers, but its biological role in PCa is still unclear.
Methods: This study extracted 98 reliable PMGs, and analyzed their somatic mutations, expression levels, and prognostic significance.
Viruses
November 2024
Department of Virology 1, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Herpes simplex virus type 1 (HSV-1) acyclovir (ACV) resistance is acquired by mutations in the viral thymidine kinase (TK) or DNA polymerase (DNApol) genes. We previously obtained an ACV-resistant clone (HSV-1_VZV_TK_clone α) by sequential passages of HSV-1_VZV-TK, a recombinant virus which lacked its endogenous TK activity and instead expressed the varicella-zoster virus (VZV) TK ectopically. HSV-1_VZV_TK_clone α had been generated using an HSV-1_BAC in the presence of increasing concentrations of ACV.
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