Frailty Trajectories Following Adjuvant Chemotherapy and Mortality in Older Women With Breast Cancer

JAMA Network Open, Journal Year: 2025, Volume and Issue: 8(3), P. e250614 - e250614

Published: March 12, 2025

Importance Frailty assessed at a single time point is associated with mortality in older women breast cancer. Little known about how changes frailty following cancer treatment initiation affect mortality. Objective To evaluate the association between claims-based trajectories adjuvant chemotherapy and 5-year stage I to III Design, Setting, Participants This longitudinal cohort study used Surveillance, Epidemiology, End Results registries linked Medicare claims data (claims from 2003-2019). Women aged 65 years or diagnosed 2004 2017 were included. Eligible underwent surgery followed by as initial treatment. A landmark design was identify during year initiation. Continuous enrollment fee-for-service 180 days before diagnosis through 360 (landmark) required. who died disenrolled excluded. Analyses conducted September 2022 March 2024. Exposures Claims-based identified using Faurot index, validated proxy for based on demographics diagnosis, procedure, durable medical equipment claims. The index calculated every 30 (360 after initiation). trajectory clusters K-means clustering. Main Outcomes Measures Associations estimated Kaplan-Meier analysis. In total, 20 292 (median [IQR] age, 70 [67-74] years) identified. analysis resulted 6 clusters: 3 robust (16 120 [79.4%]) resilient (3259 [16.1%]) nonresilient (913 [4.5%]). Five-year higher belonging compared those (52.1% vs 20.3%; difference, 31.8%; 95% CI, 29.0%-36.2%). Conclusions Relevance this of cancer, long-term survival. Future research should assess interventions survival patient-centered outcomes population.

Language: Английский

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Dehydrodiisoeugenol targets the PLK1-p53 axis to inhibit breast cancer cell cycle

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Introduction There are about 2,300,000 new cases of breast cancer worldwide each year. Breast has become the first most common in world and leading cause death among women. At same time, chemotherapy resistance patients with advanced is still a serious challenge. Alpinia Katsumadai Hayata (AKH), as traditional Chinese herbal medicine, wide range pharmacological activities. Related studies have found that many compounds AKH anti-breast activity. However, it worth exploring which component main active inhibiting its mechanism action. Methods In this study, dehydrodiisoeugenol (DHIE) was screened ingredient against based on LC-MS combined drug similarity disease enrichment analysis. WGCNA, network pharmacology, molecular docking, transcriptome sequencing analysis, immune infiltration analysis single-cell were used to explore DHIE cancer. CCK-8, flow cytometry Western blot verify results vitro . The efficacy drugs verified vivo by constructing subcutaneous tumor-bearing mouse model. Results Our research showed enriched core gene targets mainly act epithelial cells tissues significantly inhibit growth affecting PLK1-p53 signaling axis arrest cell cycle at G0/G1 phase. Further although had opposite regulatory effects different isoforms p53 types cells, they eventually caused arrest. addition, reduced tumor burden, level proliferation-related marker Ki-67, inhibited expression PLK1 model, further enhanced when DOX. Discussion Collectively, our study suggests AHK may induce regulating axis, provide therapeutic strategy for specific mechanisms regulates subtypes advantages chemotherapeutic combinations compared other exploring.

Language: Английский

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Enhanced antitumor efficacy of bispecific antibody blocking PD-L1 and LAG-3 with doxorubicin: mechanism and safety evaluation

Breast Cancer Research and Treatment, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Language: Английский

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Classical and non-classical effects of angiotensin converting enzyme: how increased ACE enhances myeloid immune function.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(6), P. 107388 - 107388

Published: May 17, 2024

As part of the classical renin-angiotensin system, peptidase angiotensin-converting enzyme (ACE) makes angiotensin II which has myriad effects on systemic cardiovascular function, inflammation, and cellular proliferation. Less well known is that macrophages neutrophils make ACE in response to immune activation marked myeloid cell function independent II. Here, we discuss both (angiotensin) nonclassical functions highlight mice called 10/10 genetic manipulation increases expression by these much more resistant models tumors, infection, atherosclerosis, Alzheimer's disease. In another model NeuACE mice, increased are infection. contrast, inhibitors reduce neutrophil killing bacteria humans. Increased induces a increase macrophage oxidative metabolism, particularly mitochondrial oxidation lipids, secondary peroxisome proliferator-activated receptor α expression, results ATP. present sperm similar metabolic effect, lack activity cells reduces motility fertilization capacity. These not due actions but an unknown molecule, probably peptide, triggers profound change metabolism function. Purifying characterizing this peptide could offer new treatment for several diseases prove potentially lucrative.

Language: Английский

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Use of indicators of systolic and diastolic functions of the left ventricle in the diagnosis of early cardiotoxicity during chemotherapy with doxorubicin: An open, prospective, nonrandomized study

Cardiosomatics, Journal Year: 2024, Volume and Issue: 15(2), P. 107 - 123

Published: Aug. 17, 2024

BACKGROUND: The search for new markers of early cardiotoxicity (CT) may help reduce the incidence severe complications in cardiovascular system during chemotherapy with doxorubicin. AIM: To determine echocardiography (EchoCG) parameters potential as CT patients primary breast cancer (BC) 12 months after end MATERIAL AND METHODS: An open, prospective, nonrandomized study included 100 verified BC who were treated at Grodno University Clinic (Grodno, Belarus). Twelve chemotherapy, 10 excluded from general group (7 women refused inclusion, global longitudinal deformation myocardium could not be measured 3 because a poor acoustic window). All underwent transthoracic assessment systolic and diastolic myocardial function before chemotherapy. RESULTS: In 24/90 (26.6%) patients, relative (before / months) decrease deformity 12% (cardiotoxicity manifestation, CT+ subgroup) was detected. cutoff point absolute 18.0% (sensitivity, 87.9%; specificity, 83.7%). Significant differences found between values CT− (without manifestations) subgroups chemotherapy: indexed final volume (FDV) 54 (49; 61) 61 (53; 65) (p=0.034), (FSV) 17 (15; 20) 20 (17; 23) (p=0.031), ratio rates peaks late filling left ventricle (E/A) 1.13 (1.10; 1.27) 1.29 (1.15; 1.45) (p=0.031). sensitivity, points these established. cutoff, specificity 57.7 62.1%, 66.7% FDV; 18.8, 60.6%, 62.5% FSV; 1.18, 68.2%, E/A, respectively. CONCLUSION: FDV, FSV are candidate doxorubicin BC.

Language: Английский

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Doxorrubicina Versus Trastuzumabe: uma análise da cardiotoxicidade

Brazilian Journal of Health Review, Journal Year: 2024, Volume and Issue: 7(4), P. e72363 - e72363

Published: Aug. 29, 2024

Introdução: Cardiotoxicidade é um efeito colateral, imediato ou a longo prazo, causado pelo tratamento quimioterápico para combater neoplasias. Quimioterápicos da classe das antraciclinas, como doxorrubicina e/ou dos anticorpos monoclonais, o trastuzumabe, são altamente cardiotóxicos. Os efeitos cardiovasculares podem se manifestar com disfunção cardiovascular assintomática, insuficiência cardíaca (IC) e redução fração de ejeção do ventrículo esquerdo (FEVE). Portanto, quimioterapia diminui qualidade vida pacientes e, por isso, estudos têm buscado entender melhor esse procurando meios preventivos terapêuticos reverter tal condição. Objetivo: Proporcionar uma visão comparativa abrangente sobre cardiotoxicidade Doxorrubicina Trastuzumabe, abordando os mecanismos fundamentais resultados coletados casos câncer mama. Metodologia: Revisão integrativa literatura levantamento bibliográfico realizado partir análise artigos publicados nas bases dados Medline (Via PubMed) LILACS BVS), incluídos trabalhos que apresentavam combinações descritores Cardiotoxicity AND Doxorubicin Trastuzumab, últimos 5 anos. Resultados/Discussão: A Doxorrubicina, apesar possuir alta eficácia no combate ao mama, demonstra prazo dose-dependente, mesmo em doses pequenas. Essa intoxicação cursa FEVE desenvolvimento IC. O Trastuzumabe padrão mama positivo receptor 2 fator crescimento epidérmico humano (HER2+) também induz IC menor proporção, porém forma mais precoce, sugerindo distintos cada droga. associação assim comorbidades cardíacas pré-existentes, aumenta vezes risco relação uso isolado quimioterapia. Um observou introdução Lapatinibe Pertuzumabe, terapia combinada, possui possível cardioprotetor. Conclusão: apresenta desafios devido cardiotoxicidade, impactando na saúde pacientes, principalmente quando há combinação desses medicamentos. Terapias alternativas, ser exploradas Essas considerações sublinham necessidade pesquisas desenvolver estratégias terapêuticas seguras, priorizando preservação pós-tratamento.

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