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1/15/26

ABSTRACT

Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.

PMID:37242146 | PMC:PMC10222243 | DOI:10.3390/nu15102259

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PubMed articles on: Cancer & VTE/PE

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State

West Afr J Med. 2023 May 27;40(5):533-540. ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated.

OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer.

METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23.

RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001).

CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events.

CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d’évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d’une thromboprophylaxie. Les scores de risque des patients dans notre environnement n’ont pas été étudiés de manière adéquate.

OBJECTIF: L’étude évalue l’association des scores d’évaluation du risque thrombotique (en utilisant l’outil modifié d’évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d’un cancer lymphoïde.

MÉTHODES: Il s’agit d’une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d’Anambra). Quarante-cinq patients atteints d’un cancer lymphoïde et 45 sujets apparemment sains ont participé à l’étude. Le score modifié d’évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l’estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23.

RÉSULTATS: L’âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que l[...]

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PubMed articles on: Cancer & VTE/PE

Evaluation of Patient Characteristics Linked to Major Bleeding Events in Patients Prescribed Direct Oral Anticoagulants

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231172765. doi: 10.1177/10760296231172765.

ABSTRACT

INTRODUCTION: Direct oral anticoagulants (DOACs) demonstrated similar efficacy and lower risk of intracranial hemorrhage than warfarin in patients with atrial fibrillation and venous thromboembolism. Given the lack of data identifying risk factors in patients who bled while on a DOAC, we sought to investigate these characteristics.

MATERIALS AND METHODS: This retrospective chart review was approved by the Mass General Brigham Institutional Review Board and assessed patients who experienced bleeding events while on DOAC therapy from 6/1/2015 to 7/1/2020. Patient characteristics were evaluated, including age, sex, body mass index (BMI), renal function, concomitant therapies, and baseline comorbidities.

RESULTS: Eighty-seven patients were included for analysis, with a median age of 75.8 years. Most patients were female (51.7%) and 24 (27.6%) had a BMI >30. At time-of-event, 21 patients (24.1%) had acute kidney injury. Thirty-three patients (37.9%) were on concomitant antiplatelet therapy (APT), with 31 (35.6%) on single APT and 2 on dual APT. Pertinent comorbidities included hypertension (74.7%), ischemic cerebrovascular accident (28.7%), thyroid abnormality (23.0%), active cancer (14.9%), and anemia (13.8%). Eleven patients (12.6%) had a prior bleeding event. Most patients were on apixaban (69.0%) for the indication of stroke prevention in nonvalvular atrial fibrillation/flutter (72.4%). FDA-approved dosing was used in most patients (92.0%), and all deviations reflected underdosing. Most bleeding events were defined as major (95.4%), occurred at a critical organ site (72.4%), and developed spontaneously (58.6%).

CONCLUSIONS: These data provide insight into characteristics of patients who experience bleeding events while on DOAC therapy. Understanding these potential risk factors may optimize the safe use of these agents.

PMID:37246422 | DOI:10.1177/10760296231172765

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PubMed articles on: Cancer & VTE/PE

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns

J Bronchology Interv Pulmonol. 2023 May 29. doi: 10.1097/LBR.0000000000000930. Online ahead of print.

ABSTRACT

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS.

METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record.

RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality.

CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.

PMID:37246305 | DOI:10.1097/LBR.0000000000000930

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es témoins sont 25 (55,6 %) hommes et 20 (44,4 %) femmes. Le lymphome non hodgkinien était le néoplasme lymphoïde le plus fréquent (18, 40 %), suivi du myélome multiple (10, 22 %), de la LLC (9, 20 %), de la LAL (6, 13 %) et du lymphome hodgkinien (2, 4 %). Trente-cinq (77,8 %) sujets atteints de néoplasmes lymphoïdes présentaient un score de risque intermédiaire et 10 (22,2 %) un score de risque élevé. Dix-neuf (42,2 %) des témoins présentaient un risque intermédiaire et 26 (57,8 %) un risque faible. Les différences de proportion étaient statistiquement significatives (p < 0,001). Les niveaux médians (IQR) de P-sélectine soluble étaient significativement plus élevés chez les patients atteints de néoplasme lymphoïde (12,2 vs. 7,0 ng/mL, p <0,001).

CONCLUSION: Les tumeurs malignes lymphoïdes sont associées à des scores de risque thrombotique, des taux de sP-sélectine et des événements thromboemboliques veineux relativement plus élevés.

MOTS-CLÉS: Malignité lymphoïde, Thrombose, P-sélectine soluble, Scores d’évaluation du risqué.

PMID:37247203