Dataset Information

Translational Windows in Chordoma: A Target Appraisal.

ABSTRACT: Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in cell-cycle regulation and chromatin remodeling genes have been identified in chordomas, but their significance remains unknown. Investigation of the immune microenvironment of these tumors suggests that checkpoint protein expression may influence prognosis, and adjuvant immunotherapy may improve patient outcome. Finally, growing evidence supports aberrant growth factor signaling as potential pathogenic mechanisms in chordoma. In this review, we characterize the impact on treatment opportunities offered by the genomic and immunologic landscape of this tumor.

SUBMITTER: Hoffman SE

PROVIDER: S-EPMC7360834 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Translational Windows in Chordoma: A Target Appraisal.

Hoffman Samantha E SE Al Abdulmohsen Sally A SA Gupta Saksham S Hauser Blake M BM Meredith David M DM Dunn Ian F IF Bi Wenya Linda WL

Frontiers in neurology 20200708

Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in ...[more]

PMID: 32733369

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Project description:IntroductionDespite hypertension guidelines suggest that the most effective treatment strategy to improve blood pressure (BP) target achievement is to implement the use of combination treatment, monotherapy is still widely used in the clinical practice of hypertension.AimTo investigate BP control under monotherapy in the setting of real-life.MethodsWe extracted data from a medical database of adult outpatients who were referred to the Hypertension Unit, Sant'Andrea Hospital, Rome (IT), including anthropometric data, CV risk factors and comorbidities, presence or absence of antihypertensive therapy and concomitant medications. Among treated hypertensive patients, we identified only those under single antihypertensive agent (monotherapy). Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: (a) < 130/80 mmHg in individuals aged 18-65 years; (b) < 140/80 mmHg in those aged > 65 years.ResultsFrom an overall sample of 7797 records we selected 1578 (20.2%) hypertensive outpatients (47.3% female, age 59.5 ± 13.6 years, BMI 26.6 ± 4.4 kg/m2) treated with monotherapies, among whom 30.5% received ACE inhibitors, 37.7% ARBs, 15.8% beta-blockers, 10.6% CCBs, 3.0% diuretics, and 2.0% alpha-blockers. 36.6% of these patients reached the conventional clinic BP goal of < 140/90 mmHg, whilst the 2018 European guidelines BP treatment targets were fulfilled only in 14.0%. In particular, 10.2% patients aged 18-65 years and 20.4% of those aged > 65 years achieved the recommended BP goals. All these proportions results significantly lower than those achieved with dual (18.2%) or triple (22.2%) combination therapy, though higher than those obtained with life-style changes (10.8%). Proportions of patients on monotherapies with normal home and 24-h BP levels were 22.0% and 30.2%, respectively, though only 5.2% and 7.3% of these patients achieved sustained BP control, respectively. Ageing and dyslipidaemia showed significant and independent positive predictive value for the achievement of the recommended BP treatment targets, whereas European SCORE resulted a negative and independent predictor in outpatients treated with monotherapies.ConclusionsOur data showed a persistent use of monotherapy in the clinical practice, though with unsatisfactory BP control, especially in light of the BP treatment targets suggested by the last hypertension guidelines.

Dataset Information

Translational Windows in Chordoma: A Target Appraisal.

Publications

Translational Windows in Chordoma: A Target Appraisal.

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