Long Survival and Severe Toxicity Under 5-Fluorouracil–Based Therapy in a Patient With Colorectal Cancer Who Harbors a Germline Codon-Stop Mutation in TYMS

Beltrán, Emilia Balboa; Duran, Goretti; Lamas, María Jesús; Carracedo, Ángel; Barros, Francisco

doi:10.1016/j.mayocp.2015.05.005

Cited by 8 publications

(4 citation statements)

References 41 publications

(55 reference statements)

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“…TYMS is an essential enzyme involved in DNA replication and repair, which serves an important role in the biosynthesis of deoxythymidine monophosphate (dTMP) (17). The association between TYMS and tumors has been reported previously.…”

Section: Discussionmentioning

confidence: 90%

Identification of TYMS as a promoting factor of retroperitoneal liposarcoma progression: Bioinformatics analysis and biological evidence

et al. 2020

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Retroperitoneal liposarcoma (RLPS) is one of the most common types of retroperitoneal sarcomas, and has a high recurrence rate. There is an urgent need to further explore its pathogenesis and develop more effective treatment strategies. The aim of the present study was to identify potential driver genes of RLPS through bioinformatics analysis and molecular biology to elucidate potential targets that are suitable for further analysis for the treatment of RLPS. Differentially expressed genes (DEGs) between liposarcoma and normal fatty (NF) tissues were identified based on microarray data through bioinformatics analysis, and thymidylate synthase (TYMS) was selected from the DEGs, based on high content screening (HCS). TYMS expression was evaluated in RLPS tumor tissues and cell lines. A total of 21 RLPS tissues and 10 NF frozen tissues were used for reverse transcription-quantitative PCR, and 47 RLPS formalin-fixed specimens were used for immunohistochemical analysis. The effect of TYMS downregulation on cell proliferation, apoptosis, cell cycle progression, and cell migration and invasion were evaluated using lentivirus-mediated short hairpin RNA. The underlying mechanisms of TYMS in RLPS were examined by protein microarray and verified by western blotting. A total of 855 DEGs were identified. TYMS knockdown had the most notable effect on the proliferative capacity of RLPS cells according to the HCS results. TYMS mRNA expression levels were higher in RLPS tissues compared with NF tissues (P<0.001). TYMS expression was higher in high-grade RLPS tissues compared with low-grade RLPS tissues (P=0.003). The patients with positive TYMS expression had a worse overall survival (OS) and disease-free survival (DFS) compared with the patients with negative TYMS expression (OS, P=0.024; DFS, P= 0.030). The knockdown of TYMS reduced proliferation, promoted apoptosis, facilitated cell cycle progression from G 1 to S phase, and reduced cell migration and invasion of RLPS cells. Protein microarray analysis and western blotting showed that the Janus Kinase/Signal transducers and activators of transcription pathway was downregulated following TYMS knockdown. In conclusion, TYMS expression is upregulated in RLPS tissues, and downregulation of TYMS reduces RLPS progression.

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Section: Discussionmentioning

confidence: 90%

Identification of TYMS as a promoting factor of retroperitoneal liposarcoma progression: Bioinformatics analysis and biological evidence

et al. 2020

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“…Wnt signaling pathway, well-known functioning in the process of tumorigenesis, contributed to development, progression and metastasis of various cancers (MacDonald et al, 2009). Thymidylate synthase (TYMS), a key enzymes of 5-fluorouracil (5-FU) catabolic pathway, had been correlated with 5-FU-based therapy (Balboa-Beltran et al, 2015). Furthermore, as a result of TYMS depletion caused by miR-197, the sensitivity to 5-FU was increased .…”

Section: Mir-197 In Drug Resistancementioning

confidence: 99%

miR-197: A novel biomarker for cancers

Wang

Chen

et al. 2016

Gene

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“…The mutations in TYMS (g.657795_657826del, c.53_84del and p.Gln18Argfs*42) were reported to connect with survival of CRC 24 . A meta-analysis conducted by Jennings BA et.al 25 suggested that TYMS rs45445694 was associated with the reduced protein expression and improved clinical benefit from 5-FU.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy

Jiang

Yuan

et al. 2020

J. Cancer

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Background: Paclitaxel plays a pivotal role in the chemotherapy of breast cancer, but resistance to this drug is an important obstacle in the treatment. It is reported that microRNA-152-3p (miR-152-3p) is involved in tamoxifen resistance in breast cancer, but whether it is involved in paclitaxel resistance in breast cancer remains unknown. Materials and methods: We examined the expression of miR-152-3p in breast cancer tissues and cells by qRT-PCR. After transfecting paclitaxel-resistant MCF-7/TAX cells with miR-152-3p mimics, we analyzed the function of miR-152-3p in these cells by MTT assay and flow cytometry. We screened the target gene, endothelial PAS domain-containing protein 1 (EPAS1), using bioinformatics analysis and verified it with the dual luciferase reporter gene experiment. The relationship between EPAS1 and miR-152-3p and their roles in paclitaxel resistance of breast cancer were further investigated using RNA interference and transfection techniques. Results: The expression of miR-152-3p in normal breast tissues and cells was markedly higher than that in breast cancer. Overexpression of miR-152-3p decreased the survival rate and increased the apoptosis rate and sensitivity of MCF-7/TAX cells to paclitaxel. We confirmed that EPAS1 is the target of miR-152-3p and is negatively regulated by this miRNA. Moreover, transfection with EPAS1 siRNA enhanced the susceptibility and apoptosis rate of MCF-7/TAX cells to paclitaxel. Co-transfection of miR-152-3p mimics and EPAS1 increased paclitaxel sensitivity and apoptosis induced by the drug. Conclusion: miR-152-3p inhibits the survival of MCF-7/TAX cells and promotes their apoptosis by targeting the expression of EPAS1, thereby, enhancing the sensitivity of these breast cancer cells to paclitaxel.

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Long Survival and Severe Toxicity Under 5-Fluorouracil–Based Therapy in a Patient With Colorectal Cancer Who Harbors a Germline Codon-Stop Mutation in TYMS

Cited by 8 publications

References 41 publications

Identification of TYMS as a promoting factor of retroperitoneal liposarcoma progression: Bioinformatics analysis and biological evidence

Identification of TYMS as a promoting factor of retroperitoneal liposarcoma progression: Bioinformatics analysis and biological evidence

miR-197: A novel biomarker for cancers

Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy

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