Affinage

TYMS

Thymidylate synthase · UniProt P04818

Length
313 aa
Mass
35.7 kDa
Annotated
2026-06-10
100 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TYMS encodes thymidylate synthase, an enzyme whose expression level directly determines tumor cell sensitivity to fluoropyrimidine chemotherapy: genetic deletion of a TYMS allele in colorectal cancer cells lowers protein expression and confers hypersensitivity to 5-FU and 5-fluoro-2'-deoxyuridine, with resistance restored by re-introduction of exogenous TYMS cDNA (PMID:17018589). TYMS expression is controlled at multiple levels — transcriptionally activated by FOXM1, which binds the TYMS promoter to drive expression and 5-FU resistance (PMID:30728402, PMID:30538221), and by MYC, whose activation predetermines sensitivity to the TYMS inhibitor raltitrexed (PMID:31648989) — and post-transcriptionally repressed through 3'-UTR targeting by miR-433 (PMID:23915286), miR-140-3p (PMID:34818974), and miR-1307-3p, the last of which is itself modulated by a pre-miRNA polymorphism that elevates TYMS and confers capecitabine/5-FU resistance (PMID:29088787). Beyond its canonical role in nucleotide synthesis, elevated TYMS acts oncogenically: in an Ink4a/Arf-null mouse model TYMS overexpression accelerates tumorigenesis and metastasis and produces genomic instability, double-strand DNA damage, aneuploidy, and loss of the G1/S checkpoint, while in vivo shRNA knockdown reduces tumor incidence and prolongs survival (PMID:37106126). TYMS promotes proliferation, migration, invasion, and EMT in colorectal cancer through a TYMS-TM4SF4 axis (PMID:35411242), and its knockdown suppresses proliferation while promoting ferroptosis via inhibition of PI3K/Akt/mTOR signaling with ACSL4 upregulation and GPX4 downregulation (PMID:38961034). TYMS-derived peptides are presented on HLA-A2 and recognized by tumor-reactive cytotoxic T lymphocytes, marking the protein as a tumor-associated antigen (PMID:15355913).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2004 Medium

    Established that TYMS protein is not only an enzyme but can serve as a tumor-associated antigen, opening an immunological dimension to its role in cancer.

    Evidence Gene expression cloning, HLA-A2 peptide binding and CTL cytotoxicity assays with patient tumor-infiltrating lymphocytes

    PMID:15355913

    Open questions at the time
    • Does not address enzymatic or proliferative function
    • Clinical relevance of CTL recognition for tumor control untested
  2. 2005 Low

    Demonstrated that a TYMS 3'-UTR insertion/deletion polymorphism has functional consequences for systemic folate metabolism, linking germline TYMS variation to a measurable biochemical phenotype.

    Evidence Population genetic association study with RBC folate and homocysteine measurements

    PMID:15682292

    Open questions at the time
    • Association without direct enzymatic experiment on the protein
    • Mechanism connecting 3'-UTR variant to expression not demonstrated here
  3. 2006 High

    Resolved whether TYMS copy number/expression is causally rather than correlatively linked to fluoropyrimidine sensitivity, by directly manipulating the locus and rescuing the phenotype.

    Evidence Engineered LOH (allele deletion) plus exogenous cDNA complementation with in vitro drug sensitivity assays in a diploid colorectal cancer line

    PMID:17018589

    Open questions at the time
    • Single cell-line context
    • Does not address transcriptional/post-transcriptional regulators that set expression in tumors
  4. 2013 Medium

    Identified the first post-transcriptional brake on TYMS, showing that miRNA-mediated 3'-UTR repression lowers TYMS protein and sensitizes cells to 5-FU.

    Evidence Dual-luciferase reporter, Western blot, and proliferation assays in HeLa cells (miR-433)

    PMID:23915286

    Open questions at the time
    • Single cell line
    • Endogenous regulation of miR-433 in tumors not addressed
  5. 2019 Medium

    Defined the transcriptional inputs that drive TYMS, establishing FOXM1 as a direct promoter-binding activator and MYC as an activator whose status predetermines antifolate response.

    Evidence ChIP/ChIP-seq with siRNA knockdown and overexpression (FOXM1, colorectal and cholangiocarcinoma); genome-scale CRISPR screen with xenograft validation (MYC/NIPBL/raltitrexed)

    PMID:30538221 PMID:30728402 PMID:31648989

    Open questions at the time
    • Quantitative contribution of FOXM1 vs MYC to TYMS levels unresolved
    • How regulatory uncoupling arises in highly resistant cells not mechanistically defined
  6. 2019 Medium

    Connected TYMS (with DHFR) to growth signaling, showing combined antifolate inhibition acts through AMPK activation and mTOR suppression.

    Evidence Proliferation assays, U251 xenografts, and AMPK/mTOR Western blot (pemetrexed + temozolomide in glioma)

    PMID:31542479

    Open questions at the time
    • Whether AMPK/mTOR effects are direct TYMS consequences or secondary to drug combination unclear
    • Single tumor type
  7. 2022 Medium

    Extended TYMS function beyond nucleotide supply to invasion and EMT, identifying a downstream TYMS-TM4SF4 axis controlling EMT and stemness markers.

    Evidence siRNA knockdown with functional assays, RNA-seq, and Western blot in colorectal cancer; additional knockdown/invasion/DNA-synthesis assays in HCC

    PMID:34858842 PMID:35411242

    Open questions at the time
    • Mechanism by which TYMS regulates TM4SF4 not defined
    • HCC findings rest on a single method class
  8. 2023 High

    Provided in vivo genetic proof that TYMS overexpression is oncogenic and drives genomic instability, not merely a proliferation marker.

    Evidence Ink4a/Arf-null genetically engineered mouse model with in vivo shRNA knockdown, flow cytometry, and DNA damage assays

    PMID:37106126

    Open questions at the time
    • Molecular basis of TYMS-induced double-strand breaks and checkpoint loss not defined
    • Cooperation specific to Ink4a/Arf loss context
  9. 2024 Medium

    Linked TYMS loss to a regulated cell death program, showing knockdown promotes ferroptosis through PI3K/Akt/mTOR inhibition with ACSL4/GPX4 remodeling.

    Evidence siRNA knockdown, ROS/Fe2+ and Western blot readouts, xenograft and IHC in triple-negative breast cancer

    PMID:38961034

    Open questions at the time
    • Whether ferroptosis follows from nucleotide depletion or a distinct TYMS function unresolved
    • Direct link between TYMS and PI3K/Akt/mTOR not biochemically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TYMS enzymatic output and its non-canonical oncogenic and signaling roles are mechanistically coupled remains unresolved.
  • No structural/biochemical account in the corpus linking TYMS catalysis to genomic instability or EMT
  • Direct molecular connection of TYMS to PI3K/Akt/mTOR and AMPK/mTOR signaling unestablished
  • Mechanism of the TYMS-TM4SF4 axis undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 2
Pathway
R-HSA-1643685 Disease 2 R-HSA-1430728 Metabolism 1

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 FOXM1 transcription factor directly regulates TYMS expression in colorectal cancer cells; ChIP and ChIP-seq confirmed FOXM1 binding to the TYMS promoter, and FOXM1 knockdown decreased TYMS expression, while FOXM1 overexpression increased it, contributing to 5-FU resistance. ChIP, ChIP-seq, siRNA knockdown, overexpression studies in colon cancer cell lines Scientific reports Medium 30728402
2018 FOXM1 binds the TYMS promoter and regulates TYMS expression upon 5-FU treatment in 5-FU-sensitive cholangiocarcinoma cells (KKU-D131), but not in highly resistant HuCCA cells, demonstrating that uncoupling of the FOXM1-TYMS regulatory axis underlies severe 5-FU resistance. ChIP, siRNA knockdown, RT-qPCR, Western blot, clonogenicity assay Cell death & disease Medium 30538221
2013 miR-433 post-transcriptionally represses TYMS expression by binding the 3'-UTR of TYMS mRNA, reducing TYMS protein levels and increasing 5-FU sensitivity in HeLa cells. Dual-luciferase reporter assay, RT-PCR, Western blot, WST-8 cell proliferation assay BMC cancer Medium 23915286
2019 MYC transcriptionally upregulates TYMS expression in gastrointestinal cancer cells; MYC-driven TYMS upregulation predetermines sensitivity to the TYMS inhibitor raltitrexed. NIPBL inactivation decreases RTX therapeutic responses by blocking MYC-driven TYMS transcription. Genome-scale CRISPR-Cas9 knockout screening, cell-based functional assays, in vivo xenograft experiments EBioMedicine Medium 31648989
2021 miR-140-3p directly targets the TYMS 3'-UTR (confirmed by dual-luciferase reporter assay) and suppresses TYMS expression; miR-140-3p upregulation inhibited proliferation, migration, invasion, and angiogenesis of lung adenocarcinoma cells, effects reversed by TYMS silencing. Dual-luciferase reporter assay, qRT-PCR, Western blot, colony formation, Scratch, Transwell, tube formation assays Bioengineered Medium 34818974
2006 Genetic engineering of loss of heterozygosity (LOH) at the TYMS locus (deletion of the short 2-repeat allele) in a diploid colorectal cancer cell line reduced TS protein expression and caused hypersensitivity to 5-FU and 5-fluoro-2'-deoxyuridine; re-introduction of exogenous TYMS cDNA restored resistance, directly linking TYMS copy number and expression level to 5-FU sensitivity. Genetic engineering (allele deletion), exogenous cDNA complementation, in vitro drug sensitivity assay Cancer research High 17018589
2023 TYMS overexpression in an Ink4a/Arf-null mouse model cooperates with Ink4a/Arf loss to accelerate tumorigenesis and metastasis; TYMS-expressing tumors exhibited genomic instability (double-strand DNA damage, aneuploidy, loss of G1/S checkpoint). TYMS shRNA knockdown in vivo reduced tumor incidence, delayed progression, and prolonged survival. Genetically engineered mouse model, shRNA in vivo knockdown, flow cytometry, DNA damage assays Oncogene High 37106126
2019 TYMS and DHFR are positive regulators of glioma cell growth; inhibition of DHFR/TYMS by pemetrexed combined with temozolomide (TMZ) produced synergistic anti-glioma activity in vitro and in U251 xenografts via activation of AMPK and subsequent suppression of the mTOR signaling pathway. Cell proliferation assays, xenograft in vivo model, Western blot for AMPK/mTOR pathway European journal of pharmacology Medium 31542479
2024 TYMS knockdown in triple-negative breast cancer cells suppressed proliferation and promoted ferroptosis, associated with increased ROS and Fe2+ accumulation, upregulation of ACSL4, and downregulation of GPX4; mechanistically linked to inhibition of PI3K/Akt/mTOR signaling pathway. siRNA knockdown, Western blot, flow cytometry (ROS/apoptosis), xenograft tumor model, IHC Cell biochemistry and biophysics Medium 38961034
2022 TYMS knockdown in hepatocellular carcinoma cells inhibited growth and invasion, decreased DNA synthesis, and reduced extracellular matrix (ECM) degradation, implicating TYMS in HCC metastasis via these mechanisms. siRNA knockdown, cell invasion assay, DNA synthesis assay Frontiers in oncology Low 34858842
2022 TYMS knockdown in colorectal cancer cells inhibited proliferation, migration, and invasion, and reduced spheroid formation. TYMS promotes CRC progression by regulating EMT-related proteins (E-cadherin, Vimentin, MMP-9) and stem cell biomarkers (CD133, CD44) via a TYMS-TM4SF4 axis; TM4SF4 was identified as a downstream target of TYMS. siRNA knockdown, cell functional assays (CCK-8, migration, invasion, spheroid), RNA sequencing, Western blot American journal of cancer research Medium 35411242
2017 The rs7911488 C-allele in pre-miR-1307 leads to downregulation of miR-1307-3p, which directly targets TYMS; reduced miR-1307-3p results in elevated TYMS expression, conferring resistance to capecitabine/5-FU in colon cancer cells in vitro and in vivo. Patient genotyping, in vitro 5-FU resistance assays, in vivo xenograft, miRNA-target functional analysis Oncotarget Medium 29088787
2005 The TYMS 3'UTR insertion/deletion polymorphism (ins/del) is significantly associated with red blood cell folate and homocysteine concentrations in non-smokers; del/del homozygotes had substantially higher RBC folate and lower homocysteine compared to ins/ins or ins/del individuals, indicating a functional role of this polymorphism in folate metabolism. Population genetic association study with biochemical measurements (RBC folate, homocysteine) Human genetics Low 15682292
2004 TYMS-derived HLA-A2-binding peptides were recognized by cytotoxic T lymphocytes (CTLs) from colon cancer patients, demonstrating that TYMS protein is presented as a tumor-associated antigen on HLA-A2+ colon cancer cells and can elicit tumor-reactive CTL responses. Gene expression cloning, HLA-A2 peptide binding assay, CTL cytotoxicity assay with tumor-infiltrating lymphocytes Clinical cancer research Medium 15355913

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 128 27461082
2019 FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression. Scientific reports 110 30728402
2008 The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway. Experimental brain research 110 18259738
2014 A model of TMS-induced I-waves in motor cortex. Brain stimulation 104 24680789
2003 Pharmacology of TMS. Supplements to Clinical neurophysiology 103 14677399
2015 Deep TMS on alcoholics: effects on cortisolemia and dopamine pathway modulation. A pilot study. Canadian journal of physiology and pharmacology 100 25730614
2020 State-Dependent TMS over Prefrontal Cortex Disrupts Fear-Memory Reconsolidation and Prevents the Return of Fear. Current biology : CB 98 32735813
2021 TMS-EEG signatures of glutamatergic neurotransmission in human cortex. Scientific reports 97 33854132
2007 Evidence for fast signals and later processing in human V1/V2 and V5/MT+: A TMS study of motion perception. Journal of neurophysiology 93 17634339
2023 Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: A randomized double-blind trial and TMS-EEG study. Cell reports. Medicine 91 37263267
2014 A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS. Gut 89 24647007
2017 Assessing cerebellar brain inhibition (CBI) via transcranial magnetic stimulation (TMS): A systematic review. Neuroscience and biobehavioral reviews 87 29208533
2017 The impact of GABAergic drugs on TMS-induced brain oscillations in human motor cortex. NeuroImage 80 28917695
2018 Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS-EEG study. Human brain mapping 76 30549127
2008 Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study. Carcinogenesis 69 18669903
2021 Resting fMRI-guided TMS results in subcortical and brain network modulation indexed by interleaved TMS/fMRI. Experimental brain research 61 33560448
2018 Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials. Brain stimulation 59 29572124
2018 GABA levels and measures of intracortical and interhemispheric excitability in healthy young and older adults: an MRS-TMS study. Neurobiology of aging 58 29494863
2009 Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a case-control study. Oncology reports 57 19885596
2013 MicroRNA-433 negatively regulates the expression of thymidylate synthase (TYMS) responsible for 5-fluorouracil sensitivity in HeLa cells. BMC cancer 51 23915286
2023 The VLPFC-Engaged Voluntary Emotion Regulation: Combined TMS-fMRI Evidence for the Neural Circuit of Cognitive Reappraisal. The Journal of neuroscience : the official journal of the Society for Neuroscience 48 37507228
2018 TMS demonstrates that both right and left superior temporal sulci are important for facial expression recognition. NeuroImage 48 30130641
2013 TMS over M1 reveals expression and selective suppression of conflicting action impulses. Journal of cognitive neuroscience 46 24047384
2015 Germline TYMS genotype is highly predictive in patients with metastatic gastrointestinal malignancies receiving capecitabine-based chemotherapy. Cancer chemotherapy and pharmacology 45 25677447
2012 Measuring GABAergic inhibitory activity with TMS-EEG and its potential clinical application for chronic pain. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 45 22744222
2007 Thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) polymorphisms in the Korean population for prediction of 5-fluorouracil-associated toxicity. Therapeutic drug monitoring 44 17417073
2020 The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex. Scientific reports 42 32081901
2011 Influence of polymorphisms in MTHFR 677 C→T, TYMS 3R→2R and MTR 2756 A→G on NSCLC risk and response to platinum-based chemotherapy in advanced NSCLC. Pharmacogenomics 38 21605004
2005 A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations. Human genetics 38 15682292
2014 Role of key TYMS polymorphisms on methotrexate therapeutic outcome in portuguese rheumatoid arthritis patients. PloS one 37 25279663
2019 Task-related measures of short-interval intracortical inhibition and GABA levels in healthy young and older adults: A multimodal TMS-MRS study. NeuroImage 36 31863914
2013 Current approaches for TYMS polymorphisms and their importance in molecular epidemiology and pharmacogenetics. Pharmacogenomics 35 23930679
2013 Association between TYMS expression and efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer: a meta-analysis. PloS one 35 24040222
2016 Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia. Frontiers in neural circuits 34 27891079
2024 Mechanisms of Action of TMS in the Treatment of Depression. Current topics in behavioral neurosciences 33 38844713
2015 Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR , TYMS, and TCII genes and the efficacy and toxicity of methotrexate treatment in patients with rheumatoid arthritis. Polskie Archiwum Medycyny Wewnetrznej 33 25599563
2009 Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: A challenge or a dilemma? Clinical colorectal cancer 33 19822515
2017 Cortical inhibition assessed using paired-pulse TMS-EEG is increased in older adults. Brain stimulation 32 29317185
2016 Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance. Cancer chemotherapy and pharmacology 32 26842788
2013 Top-down interference and cortical responsiveness in face processing: a TMS-EEG study. NeuroImage 32 23523809
2023 Effects of transcranial magnetic stimulation (TMS) current direction and pulse waveform on cortico-cortical connectivity: A registered report TMS-EEG study. The European journal of neuroscience 31 37649453
2020 Investigating high- and low-frequency neuro-cardiac-guided TMS for probing the frontal vagal pathway. Brain stimulation 31 32205066
2004 Two proliferation-related proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+ colon cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 31 15355913
2007 Polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and thymidylate synthase (TYMS) in multiple myeloma risk. Leukemia research 30 17655928
2006 Genomic copy number changes affecting the thymidylate synthase (TYMS) gene in cancer: a model for patient classification to aid fluoropyrimidine therapy. Cancer research 30 17018589
2019 Pharmacological mechanisms of interhemispheric signal propagation: a TMS-EEG study. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 29 31357206
2016 Abnormal corticospinal tract function and motor cortex excitability in non-ataxic SCA2 mutation carriers: A TMS study. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 29 27417041
2022 FOXM1-induced TYMS upregulation promotes the progression of hepatocellular carcinoma. Cancer cell international 28 35093082
2022 Cerebellar noninvasive neuromodulation influences the reactivity of the contralateral primary motor cortex and surrounding areas: a TMS-EMG-EEG study. Cerebellum (London, England) 27 35355218
2019 DHFR/TYMS are positive regulators of glioma cell growth and modulate chemo-sensitivity to temozolomide. European journal of pharmacology 26 31542479
1994 Liposomal N,N,N-trimethylsphingosine (TMS) as an inhibitor of B16 melanoma cell growth and metastasis with reduced toxicity and enhanced drug efficacy compared to free TMS: cell membrane signaling as a target in cancer therapy III. Cancer research 26 8174128
2012 Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS). BMC cancer 25 22866924
2010 The association between two polymorphisms in the TYMS gene and breast cancer risk: a meta-analysis. Breast cancer research and treatment 25 21188629
2009 MTHFR and TYMS genotypes influence TPMT activity and its differential modulation in males and females. Clinical biochemistry 25 19748501
2022 Assessing effective connectivity of the cerebellum with cerebral cortex using TMS-EEG. Brain stimulation 24 36180039
2019 MYC predetermines the sensitivity of gastrointestinal cancer to antifolate drugs through regulating TYMS transcription. EBioMedicine 24 31648989
2018 FOXM1 modulates 5-fluorouracil sensitivity in cholangiocarcinoma through thymidylate synthase (TYMS): implications of FOXM1-TYMS axis uncoupling in 5-FU resistance. Cell death & disease 24 30538221
2014 Expression of ERCC1, TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal squamous cell carcinoma: A hierarchical clustering analysis. Experimental and therapeutic medicine 24 24926347
2010 Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 24 20570913
2021 A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia. Journal of psychiatry & neuroscience : JPN 23 34933940
2010 Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. Cancer epidemiology 23 20638924
2023 TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background. Oncogene 22 37106126
2023 Intracortical and intercortical networks in patients after stroke: a concurrent TMS-EEG study. Journal of neuroengineering and rehabilitation 22 37533093
2022 Repetitive transcranial magnetic stimulation (r-TMS) and selective serotonin reuptake inhibitor-resistance in obsessive-compulsive disorder: A meta-analysis and clinical implications. Comprehensive psychiatry 22 35917621
2022 The reliability of two prospective cortical biomarkers for pain: EEG peak alpha frequency and TMS corticomotor excitability. Journal of neuroscience methods 22 36495945
2020 Copper-Mediated DNA-Compatible One-Pot Click Reactions of Alkynes with Aryl Borates and TMS-N3. Organic letters 22 32383596
2018 Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population. Frontiers in pharmacology 22 30546311
2019 Evaluating the role of ENOSF1 and TYMS variants as predictors in fluoropyrimidine-related toxicities: An IPD meta-analysis. Pharmacological research 21 31838077
2023 Directional sensitivity of cortical neurons towards TMS-induced electric fields. Imaging neuroscience (Cambridge, Mass.) 20 40799717
2022 TYMS-TM4SF4 axis promotes the progression of colorectal cancer by EMT and upregulating stem cell marker. American journal of cancer research 20 35411242
2020 Dual-site TMS demonstrates causal functional connectivity between the left and right posterior temporal sulci during facial expression recognition. Brain stimulation 20 32335230
2019 TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer. World journal of gastrointestinal oncology 20 31367274
2019 Expression of ERCC1 and TYMS in colorectal cancer patients and the predictive value of chemotherapy efficacy. Oncology letters 20 31423175
2014 Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy. Molecular medicine reports 19 25573098
2021 MicroRNA-140-3p represses the proliferation, migration, invasion and angiogenesis of lung adenocarcinoma cells via targeting TYMS (thymidylate synthetase). Bioengineered 18 34818974
2018 The role of genetic polymorphisms in the thymidylate synthase (TYMS) gene in methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. Pharmacogenetics and genomics 18 30222710
2017 Rs7911488 modified the efficacy of capecitabine-based therapy in colon cancer through altering miR-1307-3p and TYMS expression. Oncotarget 17 29088787
2011 Inhibition of proliferation and induction of apoptosis by trimethoxyl stilbene (TMS) in a lung cancer cell line. Asian Pacific journal of cancer prevention : APJCP 17 22296367
2005 TYMS and DPYD polymorphisms in a Turkish population. European journal of clinical pharmacology 17 16328315
2021 Transcranial direct current stimulation improve symptoms and modulates cortical inhibition in obsessive-compulsive disorder: A TMS-EEG study. Journal of affective disorders 16 34801604
2019 Polymorphisms of MTHFR and TYMS predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer. Cancer communications (London, England) 16 31601265
2019 Blood mRNA expression of REV3L and TYMS as potential predictive biomarkers from platinum-based chemotherapy plus pemetrexed in non-small cell lung cancer patients. Cancer chemotherapy and pharmacology 16 31832811
2017 Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer. BMC gastroenterology 16 28056823
2022 Mosloflavone-Resveratrol Hybrid TMS-HDMF-5z Exhibits Potent In Vitro and In Vivo Anti-Inflammatory Effects Through NF-κB, AP-1, and JAK/STAT Inactivation. Frontiers in pharmacology 15 35529447
2016 Autoantibodies against TYMS and PDLIM1 proteins detected as circulatory signatures in Indian breast cancer patients. Proteomics. Clinical applications 15 27068564
2013 mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in postoperative patients with non-small cell lung cancer. Asian Pacific journal of cancer prevention : APJCP 15 23803067
2013 Alterations in the expression pattern of MTHFR, DHFR, TYMS, and SLC19A1 genes after treatment of laryngeal cancer cells with high and low doses of methotrexate. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 23838799
2023 Complementary contribution of the medial and lateral human parietal cortex to grasping: a repetitive TMS study. Cerebral cortex (New York, N.Y. : 1991) 14 36245221
2020 Individualized chemotherapy guided by the expression of ERCC1, RRM1, TUBB3, TYMS and TOP2A genes versus classic chemotherapy in the treatment of breast cancer: A comparative effectiveness study. Oncology letters 14 33240427
2013 DPYD, TYMS, TYMP, TK1, and TK2 genetic expressions as response markers in locally advanced rectal cancer patients treated with fluoropyrimidine-based chemoradiotherapy. BioMed research international 14 24455740
2023 The CBIT + TMS trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics. Trials 13 37400828
2015 Expression of TYMS in lymph node metastasis from low-grade glioma. Oncology letters 13 26622711
2024 Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study. Brain research bulletin 12 38710310
2024 TYMS Knockdown Suppresses Cells Proliferation, Promotes Ferroptosis via Inhibits PI3K/Akt/mTOR Signaling Pathway Activation in Triple Negative Breast Cancer. Cell biochemistry and biophysics 12 38961034
2018 TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A gene mutation in Mexican colorectal cancer patients. Acta biochimica Polonica 12 29906295
2012 Thymidylate synthase gene (TYMS) polymorphisms in sporadic and hereditary breast cancer. BMC research notes 12 23217244
2006 Fourteen novel genetic variations and haplotype structures of the TYMS gene encoding human thymidylate synthase (TS). Drug metabolism and pharmacokinetics 12 17220568
2024 ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target. Frontiers in immunology 11 38558817
2021 Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma. Frontiers in oncology 11 34858842
2011 Relationship between TYMS and ERCC1 mRNA expression and in vitro chemosensitivity in colorectal cancer. Anticancer research 11 22110208

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