Thymidine kinase 1 expression defines an activated G1 state of the cell cycle as revealed with site-specific antibodies and ArrayScan™ assays

Gasparri, Fabio; Wang, Naining; Skog, Sven; Galvani, Arturo; Eriksson, Staffan

doi:10.1016/j.ejcb.2009.06.005

Cited by 50 publications

(54 citation statements)

References 18 publications

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“…We noted no decrease of Ki67 staining in the BEZ235 treatment groups relative to Ctrl-treated animals (data not shown). As an alternative marker for tumor cell proliferation, TK1 activity has been reported to be linked to cell proliferation (34). Additionally, TK1 is detected in serum of tumor patients and correlates with clinical stage and tumor prognosis (34).…”

Section: Modulation Of Pi3k/mtor Pathway Proteins Does Not Correlate mentioning

confidence: 99%

Gastric Cancer Growth Control by BEZ235In VivoDoes Not Correlate with PI3K/mTOR Target Inhibition but with [18F]FLT Uptake

Fuereder

Wanek²,

Pflegerl³

et al. 2011

Clinical Cancer Research

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Purpose: In this study, we tested the antitumor activity of the dual phosphoinositide 3-kinase (PI3K)/ mTOR inhibitor BEZ235 against gastric cancer in vitro and in vivo.Experimental Design: Gastric cancer cell lines (N87, MKN45, and MKN28) were incubated with BEZ235 and assessed for cell viability, cell cycle, and PI3K/mTOR target inhibition. In vivo, athymic nude mice were inoculated with N87, MKN28, or MKN45 cells and treated daily with BEZ235. Results: In vitro, BEZ235 dose dependently decreased the cell viability of gastric cancer cell lines. The antiproliferative activity of BEZ235 was linked to a G 1 cell-cycle arrest. In vivo, BEZ235 treatment resulted in PI3K/mTOR target inhibition as shown by dephosphorylation of AKT and S6 protein in all xenograft models. However, BEZ235 treatment only inhibited tumor growth of N87 xenografts, whereas no antitumor effect was observed in the MKN28 and MKN45 xenograft models. Sensitivity to BEZ235 in vivo correlated with downregulation of the proliferation marker thymidine kinase 1.

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Section: Modulation Of Pi3k/mtor Pathway Proteins Does Not Correlate mentioning

confidence: 99%

Gastric Cancer Growth Control by BEZ235In VivoDoes Not Correlate with PI3K/mTOR Target Inhibition but with [18F]FLT Uptake

Fuereder

Wanek²,

Pflegerl³

et al. 2011

Clinical Cancer Research

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“…TK1 is activated during the late G1 stage of the cell cycle, reaches a peak during the late S and G2 phase and is degraded during mitosis. There are two types of thymidine kinase (TK), cytoplasmic (TK1) and mitochondrial (TK2); however, the expression of the latter is not associated with cell proliferation (9,10). TK1 serum levels are determined by its activity (STK1a) or its concentration (STK1p) (8), which is determined by specific anti-TK1 antibodies (SSTK Biotech Ltd., Shenzhen, China).…”

Section: Introductionmentioning

confidence: 99%

Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

Chen

Tang

Xia

et al. 2013

Molecular and Clinical Oncology

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In this study, the use of serum thymidine kinase 1 protein (STK1p) concentration for the prognosis of the overall survival of patients with locally advanced breast cancer (n=51) following routine treatment (neoadjuvant treatment, surgery and chemotherapy) was investigated. The patients were followed up for 44 months and the STK1p values were determined by a high-sensitivity enhanced chemiluminescence (ECL) dot blot assay. The variables investigated in relation to metastasis and survival were STK1p, clinical stage, tumor size and age, by the Kaplan-Meier method, the log-rank test and Cox uni- and multivariate analyses. Patients with high STK1p values (≥2.0 pM) 3–6 months after surgery exhibited a positive correlation to clinical stage, tumor size, occurrence of metastasis and survival. The hazard risk for the development of metastatic disease and mortality among breast cancer patients was 11–12 times higher in patients with high compared to those with low STK1p values (<2.0 pM). Notably, patients with stage III/IV disease and low STK1p values exhibited statistically significantly improved survival compared to patients with high STK1p values. A multivariate Cox analysis demonstrated that the STK1p levels 6 months after surgery was the only independent prognostic factor for metastasis and survival. In conclusion, STK1p is a prognostic marker in patients with locally advanced breast cancer and it may help identify a subgroup of stage III/IV patients with improved cancer-free survival expectancy, enabling personalized treatment.

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“…However, despite the evidence supporting a correlation between changes in 18 F-flourothymidine accumulation and decreased cell cycle progression, recent studies suggest, in some cases, a disconnect between thymidine kinase levels and conventional markers of cell cycle progression, such as Ki-67 expression (53,54). Thus, as with other PET tracers, when new uses for 18 F-flourothymidine are being developed, it will be essential to understand how a given drug affects thymidine salvage (e.g., thymidine kinase expression and activity) and, subsequently, whether that effect is associated with a specific tumor phenotype.…”

Section: Nucleotide Metabolismmentioning

confidence: 98%

Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine

et al. 2017

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Comprehensive molecular analysis of individual tumors provides great potential for personalized cancer therapy. However, the presence of a particular genetic alteration is often insufficient to predict therapeutic efficacy. Drugs with distinct mechanisms of action can affect the biology of tumors in specific and unique ways. Therefore, assays that can measure drug-induced perturbations of defined functional tumor properties can be highly complementary to genomic analysis. PET provides the capacity to noninvasively measure the dynamics of various tumor biologic processes in vivo. Here, we review the underlying biochemical and biologic basis for a variety of PET tracers and how they may be used to better optimize cancer therapy.

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Thymidine kinase 1 expression defines an activated G1 state of the cell cycle as revealed with site-specific antibodies and ArrayScan™ assays

Cited by 50 publications

References 18 publications

Gastric Cancer Growth Control by BEZ235In VivoDoes Not Correlate with PI3K/mTOR Target Inhibition but with [18F]FLT Uptake

Gastric Cancer Growth Control by BEZ235In VivoDoes Not Correlate with PI3K/mTOR Target Inhibition but with [18F]FLT Uptake

Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine

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