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At least 19 recordsLinked to original sources
PubMed2026

Non-telomeric function deficiency of TERT enhances pressure overload-induced mouse cardiac remodeling by activation of CNBP-mediated THBS3/ITGB1 pathway.

Recent studies show that telomerase reverse transcriptase (TERT) possesses important new biological functions in gene transcription regulation, signal transduction, tumorigenesis, vascular development and mitochondrial DNA protection independent of the maintenance of telomere length. In this study we investigated the role and mechanisms of TERT in regulating the gene expression and signal transduction during pressure overload-induced cardiac remodeling. The first-generation TERT knockout (Tert-/-) and wild-type littermate control (Tert+/+) male mice were subjected to transverse aortic constriction (TAC) surgery to establish a pressure overload-induced cardiac remodeling model. We showed that pressure overload significantly increased TERT expression in the hearts at 8 weeks after TAC, whereas TERT deficiency remarkably exacerbated pressure overload-induced cardiac dysfunction, cardiac hypertrophy and fibrosis, and reduced the survival rate of the mice. In contrast, TERT overexpression reversed phenylephrine (PE)-stimulated cardiomyocyte hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Ttranscriptomic and proteomic analyses revealed that extracellular matrix (ECM)-receptor interaction was a key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway regulated by TERT in hemodynamic overload-induced cardiac remodeling. TERT knockdown greatly enhanced, while TERT overexpression inhibited the activation of the THBS3/ITGB1 signaling pathway, in which transcription factor cellular nucleic acid-binding protein (CNBP) played a pivotal mediating role by interacting with TERT. In conclusion, the non-telomeric function of TERT in gene transcription regulation and signaling transduction plays an important role during pressure overload-induced myocardial remodeling via modulating CNBP-mediated THBS3/ITGB1 signaling pathway, which provides new targets and strategies for the prevention and treatment of pressure overload-induced cardiac remodeling.

Animals↗
PubMed2026

TERT promoter mutations and recurrence patterns in differentiated thyroid carcinoma.

Telomerase reverse transcriptase promoter mutations (TERT) are known prognostic factors associated with poor outcomes in differentiated thyroid carcinoma (DTC). We analyzed differences in DTC recurrence patterns over time according to TERT. A retrospective review was conducted on DTC patients who achieved remission after total thyroidectomy and/or radioactive iodine treatment at Samsung Medical Center between 1994 and 2004. The sites and patterns by time of recurrence in the patients were reviewed. In total, 367 patients with a median follow-up of 14 years (interquartile range, 12-17 years) were included. Recurrence occurred in 91 patients, wherein 56 had lymph node recurrence and 35 had either local or distant recurrence. TE RT and tumor size <2 cm were independent factors for recurrence in the Cox proportional hazards analysis. In cases of TERT-wild type (WT), the recurrence rate decreased significantly over time after diagnosis, whereas in TERT-mutant type (MT), a consistently high recurrence rate was observed. In the Kaplan-Meier analysis, TERT-MT exhibited a significantly poorer disease-free survival, with continuous recurrence over time, whereas in TERT-WT, the curve showed a gradual decline. Further analysis of the overall survival among the 91 patients revealed that TERT-MT was significantly associated with a higher risk of mortality, whereas TERT-WT exhibited a slowly decreasing curve. In conclusion, TERT-MT was a significant adverse prognostic factor wherein continuous recurrence necessitates long-term follow-up. For TERT-WT, the recurrence rate decreased compared to TERT-MT, and even in cases of recurrence, the treatment outcomes are favorable.

Humans↗
PubMed2025

Aberrant TERT expression: linking chronic inflammation to hepatocellular carcinoma&#x2020;.

Telomerase reverse transcriptase (TERT), the catalytic enzyme component of telomerase, plays multiple roles in cellular biology. Its canonical function is primarily associated with telomere maintenance and genomic stability. In addition, several studies revealed critical non-canonical extra-telomeric functions of TERT in various cellular processes, including cell proliferation and survival, DNA damage response, transcription, signal transduction, and metabolic regulation, both in normal and in cancer cells. Notably, TERT is aberrantly upregulated in more than 80% of hepatocellular carcinoma (HCC) cases, making it an important target in liver cancer research. However, due to the diversity and complexity of TERT's functions in vivo, the precise mechanisms by which TERT contributes to the initiation and progression of HCC remain unclear. A recent study published in The Journal of Pathology using the Alb-Cre;TertTg mouse model and clinical HCC samples addresses the role of TERT in hepatocarcinogenesis. The study demonstrates that TERT promotes cell cycle progression and hepatocarcinogenesis by enhancing NF-&#x3ba;B promoter activity and facilitating the ubiquitination of p21. Notably, absence of functional p53 accelerates liver tumor development in TERT transgenic mice. These findings further underscore the critical role of TERT in inflammation-driven hepatocarcinogenesis and provide new insights into its underlying mechanisms. &#xa9; 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Telomerase↗
PubMed2026

Value of TERT promoter mutations for early outcomes in papillary thyroid cancer.

Telomerase reverse transcriptase (TERT) promoter mutations are associated with aggressive clinicopathological features of papillary thyroid cancer (PTC). However, their independent prognostic value remains unclear. This study aimed to evaluate the prognostic significance of TERT promoter mutations (TPMs) in predicting early treatment outcomes and event-free survival (EFS) in patients with PTC. We retrospectively analyzed a prospective cohort; patients underwent surgery at a single tertiary referral center between 2019 and 2022. Patients underwent thyroidectomy, selective postoperative radioactive iodine ablation, and levothyroxine suppression therapy. Propensity score matching (PSM, 1:1) was applied to adjust for baseline clinicopathological differences. Of 10,642 patients with available molecular data, 115 (1.1%) harbored TPMs. After PSM, 90 matched pairs of patients with TERT-wild-type and TERT-mutant tumors were analyzed. Early treatment responses at 1 and 2 years post-treatment and EFS were evaluated. Early treatment responses did not differ significantly between groups at 1 year (P = 0.212) and 2 years (P = 0.571). However, patients with TERT-mutant tumors had fewer excellent responses and higher rates of structural incomplete response. During follow-up, the TERT-mutant group experienced more recurrences and one disease-specific death. Cumulative EFS was significantly poorer in the TERT-mutant group than in the TERT-wild-type group (P = 0.022). Despite their low prevalence, TPMs were independently associated with adverse oncological outcomes, including higher rates of recurrence and mortality. TPMs may serve as valuable prognostic markers for early risk stratification in PTC.

Humans↗
PubMed2026

Cytologic and Surgical Correlation of TERT-Mutated Indeterminate Thyroid Nodules: A Case Series.

IntroductionTelomerase reverse transcriptase (TERT) promoter mutations is a relatively novel mutation that has been linked with thyroid cancers. This study examines the frequency, cytology and histo-morphologic features, and clinical outcomes of TERT-mutated indeterminate thyroid nodules.MethodsA retrospective review of Bethesda III and IV thyroid cytology specimen sent for ThyroSeq&#xae; testing (2019-2022) was performed, selecting those with TERT mutations. Demographics, cytologic features, surgical diagnoses, and follow-up data were analyzed.ResultsAmong 567 specimens tested, 12 (2%) harbored TERT mutations; 4 had TERT alone, and 8 had additional mutations. Average age of patients was 69 years (92%&#x2009;>&#x2009;50 years). Eight had surgical follow-up: 50% were malignant, 25% were benign and 25% were of uncertain malignant potential. Additionally, 62% were oncocytic nodules. Clinical follow-up showed all evaluated patients were alive without recurrences or metastases at last contact.ConclusionIn our cohort, TERT promoter mutations were rare in indeterminate thyroid nodules (2%) and frequently accompanied by additional molecular changes. It is more frequently detected in older patients. Unlike prior reports describing TERT mutations exclusively in malignant thyroid tumors, our findings encompassed a broader histological spectrum, including benign, uncertain malignant potential and malignant lesions.

Humans↗
PubMed2026

Machine Learning-Based Preoperative Predicting TERT Promoter Mutation and EGFR Gene Amplification Phenotype in IDH Wild-Type Glioblastoma Using Advanced MR Habitat Imaging.

BACKGROUND AND PURPOSE: The telomerase reverse transcriptase (TERT) gene promoter mutation is a crucial factor for identifying an isocitrate dehydrogenase (IDH) wild-type glioblastoma with poor prognosis, and the epidermal growth factor receptor (EGFR) amplification may be a potential prognostic factor. The purpose of this study was to investigate the value of the tumor habitats imaging model on advanced MRI in predicting TERT promoter mutation and EGFR gene amplification phenotype of IDH wild-type glioblastoma. MATERIALS AND METHODS: One hundred seventy-nine patients with pretreatment conventional MRI, DWI, and DSC-PWI were included. The data were divided into the training set (n=112), test set (n=29), and time-independent validation set (n=38). Based on the ADC and CBV map, the solid tumor area was split into several habitat subregions using the k-means clustering algorithm (hypovascular hypercellular area, hypervascular area, and hypovascular hypocellular area). In the training set, TERT promoter mutation and EGFR gene amplification phenotype prediction models were constructed using the random forest method. The reliability of prediction models was validated in the test and the time-independent validation sets. Receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA) were used. RESULTS: The area under the curve (AUC) of the training, test, and validation sets of the TERT promoter prediction model was 0.877, 0.783, and 0.796, respectively. The accuracy of the TERT promoter prediction model was 82.1%, 75.9%, and 76.3%, respectively. The AUCs of the 3 sets for the EGFR gene amplification status prediction model were 0.877, 0.784, and 0.878, respectively. The accuracy of the EGFR gene amplification status prediction model was 79.5%, 75.9%, and 89.5%, respectively. Moreover, the prediction probability of these models was in good agreement with the actual result. CONCLUSIONS: The tumor habitat imaging model based on advanced MRI was useful for accurately predicting TERT promoter mutation and EGFR amplification status in IDH wild-type glioblastoma.

Humans↗
PubMed2026

Clinical performance of the urine-based TERT promoter AbsoluteQ Digital PCR for non-invasive detection of bladder cancer.

Bladder cancer (BC) is the ninth most common cancer worldwide, with urothelial carcinoma accounting for approximately 90% of all cases and presenting predominantly as non-muscle-invasive disease. Due to its high recurrence rate and the need for long-term surveillance, BC is associated with the highest lifetime treatment costs per patient among all cancers, making its effective management a significant clinical and economic challenge. The most frequently identified variants in the TERT gene promoter are c.-124C>T (C228T) and c.-146C>T (C250T), located within a region characterized by high guanine-cytosine (GC) content, which makes amplification challenging. We aimed to validate the AbsoluteQ Digital PCR assay for the detection of urine-based TERT promoter variants for the diagnosis of urothelial bladder cancer and to assess its diagnostic performance in comparison with standard methods. Urine samples were collected from patients with histopathologically confirmed bladder cancer (n&#x2009;=&#x2009;58) and compared with a control group (n&#x2009;=&#x2009;55). The C228T and C250T variants were tested using the AbsoluteQ Digital PCR assay. Sensitivity, specificity, and predictive values were calculated to evaluate the performance of the assessed method. The AbsoluteQ Digital PCR demonstrated superior diagnostic performance compared to conventional Sanger sequencing for detecting TERT promoter variants, achieving a sensitivity of 89.65% (95% CI: 78.16-95.72) and a specificity of 100% (95% CI: 91.87-100), with no false positives observed. Given its robustness and clinical relevance, AbsoluteQ Digital PCR is emerging as a promising tool for non-invasive molecular diagnostics targeting TERT promoter variants.

Humans↗
PubMed1979

[The allergenic nature of p-tert-butylphenolformaldehyde resin].

Until now allergic contact dermatitis to polychloroprene glues was thought to be caused by uncondensed p-tert.-butylphenol (monomer) or by the p-tert. burylphenol formaldehyde resin molecule (polycondensate) as allergens. This opinion could not be verified. We found the following two contact allergens: 2-hydroxy-5-tert.-butylbenzyl alcohol and a four nuclear-condensate from four p-tert-butylphenol molecules linear combined by methylene bridges.

Adhesives↗
PubMed2026

Leptomeningeal Dissemination in TERT Promoter-mutant Anaplastic Pleomorphic Xanthoastrocytoma Responding to BRAF-MEK Inhibition: A Case Report.

Pleomorphic xanthoastrocytoma is a rare brain tumor that frequently harbors the oncogenic BRAF V600E mutation. Approximately 28.6%-47% of high-grade pleomorphic xanthoastrocytomas are associated with TERT promoter mutation and leptomeningeal dissemination, for which no established treatment exists and the prognosis remains poor. Combination therapy with BRAF and MEK inhibitors has demonstrated efficacy in BRAF V600E-mutant brain tumors. We report a case of a 22-year-old man with a right temporal lobe tumor initially diagnosed as World Health Organization grade 2 pleomorphic xanthoastrocytoma after gross total resection. Two years later, the tumor recurred and underwent malignant transformation to World Health Organization grade 3 pleomorphic xanthoastrocytoma. At the third resection, pathological and genomic analyses confirmed BRAF V600E mutation together with TERT promoter mutation. Following chemoradiotherapy, spinal leptomeningeal dissemination developed. After spinal irradiation, dabrafenib plus trametinib was initiated, resulting in partial radiological response and symptomatic improvement. Although regrowth occurred 10 months after initiation of targeted therapy, the patient remains alive at the time of writing. Here, we report a case of recurrent anaplastic BRAF V600E-mutant pleomorphic xanthoastrocytoma with leptomeningeal dissemination that showed a transient but clinically meaningful response to combined BRAF-MEK inhibition and spinal radiation therapy. In addition, this case raises the possibility of an association between TERT promoter mutation and leptomeningeal dissemination, although further studies are required to clarify this relationship.

BRAF V600E↗
PubMed1977

Adrenergic agents. 8.1 Synthesis and beta-adrenergic agonist activity of some 3-tert-butylamino-2-(substituted phenyl)-1-propanols.

Replacement of the benzylic hydroxyl group of N-tert-butylnorepinephrine with a hydroxymethyl substituent affords a propanolamine homologue which retains a high degree of beta-adrenergic agonist activity. As modification of the meta substituent of catecholic ethanolamines, such as N-tert-butylnorepinephrine, often provides compounds that exert a more pronounced effect in relaxing tracheobronchial smooth muscle (beta2-adrenergic agonist) than in stimulating cardiac muscle (beta1-adrenergic response), a series of 3-tert-butylamino-2-(3-substituted 4-hydroxyphenyl)-1-propanols was prepared. The 3-meta substituents included HOCH2 (1b), H2NCONH (1c), MeSO2NH (1d), H (le), and NH2 (1f). These phenylpropanolamine derivatives were compared with their phenylethanolamine counterparts in in vitro tests that measure the ability of these compounds to relax spontaneously contracted guinea pig tracheal smooth muscle (a measure of potential bronchodilating activity) and to increase the rate of contraction of a spontaneously beating guinea pig right atrial preparation (an indicator of potential cardiac stimulating activity). In these tests all of the propanolamine derivatives included in the study were less potent than their ethanolamine relatives. In both series replacement of the catecholic m-hydroxyl group with the indicated substituents usually resulted in compounds with increased selectivity for tracheobronchial vs. cardiac muscle.

Adrenergic beta-Agonists↗
PubMed1977

Rat intestinal metabolism of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate).

Everted sacs of rat small intestine metabolized crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) under in vitro conditions to form six 14C-labeled metabolites in quantities sufficient for isolation and identification. These metabolites were 4-tert-butyl-2-chlorophenyl methyl phosphoramidate (25%), 2-chloro-4(2-hydroxy-1,1-dimethylethyl)phenyl methyl methylphosphoramidate (19%), 2-[3-chloro-4-[[(methoxy) (methyl-amino)phosphoinyl]oxy]phenyl]-2-methylpropionic acid (2%), 4-tert-butyl-2-chlorophenol (0.8%) and its glucuronide (6%), and the aromatic glucuronide of 2-chloro-4(2-hydroxy-1,1-dimethylethyl)phenol (1%). These intestinal metabolites may represent precursory stages in the overall metabolism of crufomate.

Animals↗
PubMed2025

The effect of TERT promoter mutation on predicting meningioma outcomes: a multi-institutional cohort analysis.

BACKGROUND: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing. METHODS: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of the resection site, and TERTp status evaluated by Nov 1, 2024. Multi-modal profiling was used to assess TERTp mutation, focal gene alterations-including CDKN2A/B loss-and copy number alterations. An adjusted WHO grade was calculated for TERTp-mutant meningiomas, incorporating all WHO criteria except TERTp status. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to quantify the effect of TERTp mutation on the endpoints of overall survival and recurrence-free survival across adjusted WHO grade and co-occurring molecular alterations. FINDINGS: 64 (4&#xb7;3%) of 1492 meningiomas were TERTp-mutant and 1428 (95&#xb7;7%) were TERTp-wildtype. Of the TERTp-mutant meningiomas, 33 (51&#xb7;6%) were from female patients and 31 (48&#xb7;4%) were from male patients, and the overall median age was 67 years (IQR 60-75). Of the wildtype meningiomas, 965 (67&#xb7;6%) were from female patients and 463 (32&#xb7;4%) were from male patients, and the overall median age of the patients was 59 years (IQR 48-70). Data on race was inconsistently reported and thus excluded. The TERTp-mutant patients had a 5-year overall survival (49&#xb7;4% [95% CI 33&#xb7;7-72&#xb7;4]) and 5-year recurrence-free survival (27&#xb7;6% [95% CI 16&#xb7;8-45&#xb7;5]) resembling that of patients with WHO grade 3 TERTp-wildtype tumours (5-year overall survival 32&#xb7;3% [95% CI 17&#xb7;2-60&#xb7;5], p=0&#xb7;28, 5-year recurrence-free survival 14&#xb7;3% [5&#xb7;8-35&#xb7;2], p=0&#xb7;28). However, the TERTp-mutant group had heterogenous histological grading and was enriched for aggressive molecular features, with 1p loss present in 44 (77&#xb7;2%) of 57 profiled tumours and CDKN2A/B loss in 24 (41&#xb7;4%) of the 58 profiled tumours. Adjusting tumour grade revealed a subset of TERTp-mutant meningiomas that were more molecularly and clinically benign. Among TERTp-mutant tumours, CDKN2A/B loss played a defining role in stratifying tumour behaviour. Multivariable analysis confirmed this, with CDKN2A/B loss being significantly associated with shorter overall survival (HR 3&#xb7;04 [95% CI 1&#xb7;67-5&#xb7;52], p=0&#xb7;00026) and faster time to recurrence (HR 5&#xb7;22 [95% CI 3&#xb7;10-8&#xb7;79], p<0&#xb7;0001), while TERTp-mutation did not independently affect overall survival (HR 1&#xb7;00 [95% CI 0&#xb7;53-1&#xb7;87], p=0&#xb7;99) or recurrence-free survival (1&#xb7;17 [95% CI 0&#xb7;75-1&#xb7;83], p=0&#xb7;49). Sequencing for TERTp-mutation demonstrated clinical impact only among histologically WHO grade 2 meningiomas. INTERPRETATION: The indolent behaviour of certain TERTp-mutant meningiomas suggests that TERTp mutation is not sufficient to assign the most aggressive meningioma grade. Instead, TERT sequencing might offer prognostic utility in identifying high-risk cases among WHO grade 2 meningiomas. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, Friedberg Charitable Foundation, Courtney Meningioma Research Fund, Fleming Meningioma Research Fund, and the Gray Family Foundation.

Humans↗
PubMed1978

Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines.

A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.

Analgesics↗
PubMed1979

[Vitiligo from p-tert. butylphenol; a contribution to the problem of the internal manifestations of this occupational disease].

10 worker suffering from occupational vitiligo due to p-tert. butyl phenol have been observed in an Austrian resin factory. The dust concentration and its content of p-tert. butyl phenol in the working area were measured. On the basis of these results preventive measures were taken to reduce the exposure of the workers to p-test butyl phenol. In the presented cases an involvement of internal organs--as described by Rodermund et al. (1975)--could not be observed.

Air Pollutants, Occupational↗
PubMed1979

Isolation and identification of 3,3',5,5'-tetrabis(tert-butyl)stilbenequinone from polyethylene closures containing titanium dioxide and butylated hydroxytoluene.

A yellow compound was isolated from commercially available, discolored, polyethylene ophthalmic closures containing titanium dioxide and butylated hydroxytoluene (I). This compound was present at 7.46 ppm (w/w). It was identified by UV, IR, and mass spectra as 3,3',5,5'-tetrabis(tert-butyl)stilbenequinone (II), a dimer of I. Further structural confirmation was obtained by NMR. Formation of II is catalyzed by titanium dioxide.

Butylated Hydroxytoluene↗
PubMed1979

GLC determination of S-2-(3-tert-butylamino-2-hydroxypropoxy)-3-cyanopyridine in human plasma.

S-2-(3-tert-Butylamino-2-hydroxypropoxy)-3-cyanopyridine was recovered (approximately 90%) from human plasma and detected by conversion to a diheptafluorobutyryl derivative for electron-capture GLC. A homolog served as an internal standard. The method measures plasma drug concentrations at the 5-ng/ml level and is suitable for plasma analysis from humans who receive a therapeutic oral dose.

Antihypertensive Agents↗
PubMed1979

Synthesis of amino acyl adenylates using the tert-butoxycarbonyl protecting group.

Alayl, [ 14c]-alanyl, phenylalanyl, and methionyl adenylates have been synthesized in high yields and relatively good purities. Elemental analysis 1H nmr and ir spectra have been utilized for the characterization of these extremely labile compounds. The present synthesis, which uses readily available N-tert-butoxycarbonyl amino acids, is compared with previous methods.

Adenosine Monophosphate↗