topics / مواضيع

Abstract

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups (n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.

PMID: 32519553 [PubMed - as supplied by publisher]

13:54

pubmed: tutte cardiotoxicity...

Speckle-Tracking Echocardiography for Cardioncological Evaluation in Bevacizumab-Treated Colorectal Cancer Patients.

Cardiovasc Toxicol. 2020 Jun 09;:

Authors: Sonaglioni A, Albini A, Fossile E, Pessi MA, Nicolosi GL, Lombardo M, Anzà C, Ambrosio G

Abstract

Angiogenesis inhibitor Bevacizumab (BVZ) may lead to the development of adverse effects, including hypertension and cardiac ischemia. Whether assessment of changes in myocardial strain by two-dimensional speckle-tracking echocardiography (2D-STE) can be of value in detecting BVZ-mediated cardiotoxicity at an earlier stage is not known. We investigated whether 2D-STE can non-invasively detect early evidence of cardiotoxicity in metastatic colorectal cancer (mCRC) patients treated with BVZ. Between January and June 2019, 25 consecutive patients (71.8 ± 7.5 year/old, 17 males) with mCRC were prospectively enrolled. Patients underwent physical examination, blood tests, and conventional 2D-transthoracic echocardiography implemented with 2D-STE analysis, at baseline and at 3 and 6 months following treatment with BVZ (15 mg/kg every 15 days) + 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX i.v.). At 6-month follow-up, we assessed occurrence of global longitudinal strain (GLS) impairment (> 15% decrease in GLS compared with baseline) as primary end-point and a new-onset systemic hypertension (secondary end-point). On average, GLS showed a progressive significant impairment after BVZ, from - 17.4 ± 3.2% at baseline to - 16 ± 2.9% (p = 0.003) at 6-month follow-up; > 15% decrease in GLS (primary end-point) was detected in 9 patients (36%). All other strain parameters remained unchanged. New-onset systemic hypertension (secondary end-point) was diagnosed in five patients (20%). No significant changes were observed in serial high-sensitivity cardiac troponin I measurements. No patient developed significant changes in LV size or LV ejection fraction; no case of clinically symptomatic HF was observed during BVZ-treatment. Measurement of GLS by 2D-STE analysis can effectively detect BVZ-mediated cardiotoxicity at an early stage.

PMID: 32519318 [PubMed - as supplied by publisher]

13 June 2020

11:28

Cardiotoxicity News

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The Evolving Design of NIH-Funded Cardio-Oncology Studies to Address Cancer Treatment-Related Cardiovascular Toxicity.

JACC CardioOncol. 2019 Sep;1(1):105-113

Authors: Minasian L, Dimond E, Davis M, Adhikari B, Fagerstrom R, Fabian C, Floyd J, Unger JM, Douglas PS, Mustian KM, Chow EJ, Lipshultz S, Hundley WG, Armenian S, Ky B

Abstract

Cardiovascular (CV) toxicity from cancer therapy is a significant and growing concern. Conventional oncology clinical trial designs focused singularly on cancer treatment efficacy have not provided sufficient information on both CV risk factors and outcomes. Similarly, traditional CV trials evaluating standard interventions typically exclude cancer patients, particularly those actively receiving cancer therapy. Neither trial type simultaneously evaluates the balance between CV toxicity and cancer outcomes. However, there is increasing collaboration among oncologists and cardiologists to design new cardio-oncology trials that address this important need. In this review, we detail five ongoing, oncology-based trials with integrated CV endpoints. Key design features include: 1) a careful assessment of baseline risk factors for CV disease; 2) an introduction of cardioprotective interventions at various timepoints in cancer therapy; 3) a balance of the risk of subclinical CV injury with the need for ongoing cancer treatment; and 4) an understanding of the time profile for development of clinically apparent CV toxicity. Additional critical priorities in cardio-oncology clinical research include harmonization of data collection and definitions for all physician- and patient-reported exposures and outcomes.

PMID: 32529192 [PubMed]

14 June 2020

11:55

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system.

Herz. 2020 Jun 12;:

Authors: Michel L, Totzeck M, Lehmann L, Finke D

Abstract

Immune checkpoint inhibitor (ICI) therapy induces an immune response against cancer cells. Immune checkpoint inhibitor therapy has tremendously improved the prognosis for a large number of cancers, but is associated with considerable immune-related adverse events (irAEs). Cardiovascular complications from ICI therapy occur in a modest proportion of patients, but show the highest lethality rates of all ICI-related complications. While ICI-related myocarditis is the most dangerous complication, its clinical manifestation varies, e.g., asymptomatic reduction of left ventricular function, isolated increase in cardiac troponins, and arrhythmias. This review delineates current data on cardiovascular complications of ICI therapy. The effects of ICI therapy on the cardiovascular system are classified in the context of preclinical data on the biochemical and immunological function of the immune checkpoint signaling pathways in the heart and the vascular system. Incidence, suspected pathomechanisms, typical symptoms, as well as recommended diagnostics are summarized. Current therapy recommendations for ICI-related cardiotoxicity are outlined and innovative new approaches with high potential for improving outcome in ICI-related myocarditis are delineated. A better understanding of cardiovascular complications is essential for the best possible oncocardiology care of the growing number of patients undergoing ICI therapy.

PMID: 32533218 [PubMed - as supplied by publisher]

15 June 2020

12:29

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Therapeutic implications of the PP2A/MET signalling axis in doxorubicin-induced cardiotoxicity and antitumour properties.

Br J Pharmacol. 2020 Jun 14;:

Authors: Cristóbal I, Rubio J, Santos A, Luque M, Sanz-Alvarez M, Rojo F, García-Foncillas J

PMID: 32535881 [PubMed - as supplied by publisher]

12:29

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Effect of anthracycline therapy on myocardial function and markers of fibrotic remodelling in childhood cancer survivors.

Eur Heart J Cardiovasc Imaging. 2020 Jun 14;:

Authors: Mawad W, Mertens L, Pagano JJ, Riesenkampff E, Reichert MJE, Mital S, Kantor PF, Greenberg M, Liu P, Nathan PC, Grosse-Wortmann L

Abstract

AIMS: Anthracyclines are a cornerstone of paediatric cancer treatment. We aimed to quantify myocardial cardiac magnetic resonance (CMR) native T1 (NT1) and extracellular volume fraction (ECV) as markers of fibrosis in a cohort of childhood cancer survivors (CCS).

METHODS AND RESULTS: A cohort of CCS in remission underwent CMR T1 mapping. Diastolic function was assessed by echocardiography. Results were compared to a cohort of normal controls of similar age and gender. Fifty-five CCS and 46 controls were included. Both groups had similar mean left ventricular (LV) NT1 values (999 ± 36 vs. 1007 ± 32 ms, P = 0.27); ECV was higher (25.6 ± 6.9 vs. 20.7 ± 2.4%, P = 0.003) and intracellular mass was lower (37.5 ± 8.4 vs. 43.3 ± 9.9g/m2, P = 0.02) in CCS. The CCS group had lower LV ejection fraction (EF) and LV mass index with otherwise normal diastolic function in all but one patient. The proportion of subjects with elevated ECV compared to controls did not differ between subgroups with normal or reduced LV EF (22% vs. 28%; P = 0.13) and no correlations were found between LVEF and ECV. While average values remained within normal range, mitral E/E' (6.6 ± 1.6 vs. 5.9 ± 0.9, P = 0.02) was higher in CCS. Neither NT1 nor ECV correlated with diastolic function indices or cumulative anthracycline dose.

CONCLUSIONS: There is evidence for mild diffuse extracellular volume expansion in some asymptomatic CCS; myocyte loss could be part of the mechanism, accompanied by subtle changes in systolic and diastolic function. These findings suggest mild myocardial damage and remodelling after anthracycline treatment in some CCS which requires continued monitoring.

PMID: 32535624 [PubMed - as supplied by publisher]

12:29

pubmed: tutte cardiotoxicity...

Cardiovascular risks and toxicity - The Achilles heel of androgen deprivation therapy in prostate cancer patients.

Biochim Biophys Acta Rev Cancer. 2020 Jun 11;:188383

Authors: Muniyan S, Xi L, Datta K, Das A, Teply BA, Batra SK, Kukreja RC

Abstract

Androgen deprivation therapy (ADT) is the primary systemic therapy for treating locally advanced or metastatic prostate cancer (PCa). Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity. Lifespans extension, early use of ADT, and second-line treatment with next-generation androgen receptor pathway inhibitors would further extend the duration of ADT and possibly increase the risk of ADT-induced cardiotoxicity. Meanwhile, information on the molecular mechanisms underlying ADT-induced cardiotoxicity and measures to prevent it is limited, mainly due to the lack of specifically designed preclinical studies and clinical trials. This review article compiles up-to-date evidence obtained from observational studies and clinical trials, in order to gain new insights for deciphering the association between ADT use and cardiotoxicity. In addition, potential cardioprotective strategies involving GnRH receptors and second messenger cGMP are discussed.

PMID: 32535158 [PubMed - as supplied by publisher]

17 June 2020

13:30

Cardiotoxicity News

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A Case of Acute Heart Failure Following Immunotherapy for Metastatic Lung Cancer.

Cureus. 2020 May 13;12(5):e8093

Authors: Al-Obaidi A, Parker NA, Choucair K, Alderson J, Deutsch JM

Abstract

Inhibitors of cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein-1, and programmed death-ligand 1 have been shown to produce significant antitumor activity in multiple malignancies, and have become essential oncology standard-of-care therapies. Despite their success, the checkpoint inhibitors' ability to amplify the immune system response against tumor cells has been associated with a unique panel of side effects known as immune-related adverse events. The involvement of the myocardium has been reported previously, but it's remarkably uncommon. Even more noteworthy is that secondary autoimmune myocarditis and heart failure due to these medications are typically fatal.

PMID: 32542148 [PubMed]

13:30

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Analysing the risk factors of doxorubicin-associated heart failure by a retrospective study of integrated, nation-wide databases

Orv Hetil. 2020 06;161(26):1094-1102

Authors: Fogarassy G, Fogarassyné Vathy Á, Kováts T, Hornyák L, Kenessey I, Veress G, Polgár C, Forster T

Abstract

INTRODUCTION: The incidence of dilated cardiomyopathy after anthracycline chemotherapy is mainly influenced by anthracycline cumulative dose. Previous researches showed doxorubicin treatment under cumulative dose of 450 mg/m2 associated with a low incidence of heart failure. Nowadays, doxorubicin is administered with a lower dose, the development of heart failure is largely determined by other factors.

AIM: Our purpose was to identify the risk factors for heart failure due to doxorubicin therapy.

METHOD: With the use of the Hungarian financial healthcare databases merged with the National Cancer Registry, we performed a retrospective study. All the patients having confirmation for breast carcinoma between 2004 and 2015 were enrolled. The subjects with a preceding period characterized by any chemotherapy or diagnoses suggesting heart failure were excluded. Heart failure outcome event was defined by the assignment of I50 diagnosis code at hospital discharge or in autopsy reports.

STATISTICAL ANALYSIS: We used multivariate binary logistic regression to calculate odds ratios for heart failure. Besides the baseline characteristics, oncological state and cumulative doses of the chemotherapies were also taken into account.

RESULTS: Among the analysed 3288, doxorubicin-treated patients, heart failure cumulative incidence was 6.2%. Doxorubicin cumulative dose over 400 mg/m2 increased the risk. The heart failure incidence was essentially influenced by age, even over 50 years the risk rose. Diabetes mellitus and the treatments with pyrimidine-analogues, carboplatin or bevacizumab were also associated with higher risk.

CONCLUSION: By the integration of national financial and clinical databases, we could identify the risk factors for doxorubicin-associated heart failure. Orv Hetil. 2020; 161(26): 1094-1102.

PMID: 32541088 [PubMed - in process]

13:30

pubmed: tutte cardiotoxicity...

Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement.

Biomed Pharmacother. 2020 Jun 12;129:110389

Authors: Li S, Jiang M, Wang L, Yu S

Abstract

Chemotherapy with a single chemotherapeutic agent or a combined chemotherapeutic regimen is the clinically standardized treatment for almost all human cancers. Upregulated expression of cyclooxygenase (COX)-2, also known as prostaglandin-endoperoxide synthase (PTGS), is associated with human carcinogenesis and cancer progression and COX-2 inhibitors show antitumor activity in different human cancers. Thus, a combination of chemotherapeutic agents with COX-2 inhibitors has been shown to improve therapeutic effects on human cancers. This review discusses and summarizes recent advances in cancer control and treatment using various antineoplastic drugs combined with COX-2 inhibitors. These combinations showed synergistic antitumor effects. At the gene level, COX-2 inhibitors can reduce inflammatory factors thereby regulating macrophage recruitment for activating the antitumor immune microenvironment; downregulating vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis; and inhibiting the PI3K/Akt signaling pathway to induce tumor cell apoptosis. In addition, such a combination can reduce toxicity and chemoresistance and enhance radiosensitivity, although COX-2 inhibitors-related cardiotoxicity may potentially affect its use. Further in-depth investigation of these drug combinations is needed to maximize antitumor efficacy and minimize the side effects.

PMID: 32540642 [PubMed - as supplied by publisher]

13:30

pubmed: tutte cardiotoxicity...

Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis.

Circulation. 2020 Jun 16;141(24):2031-2034

Authors: Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zubiri L, Chen CL, Sullivan RJ, Alvi RM, Rokicki A, Murphy SP, Jones-O'Connor M, Heinzerling LM, Barac A, Forrestal BJ, Yang EH, Gupta D, Kirchberger MC, Shah SP, Rizvi MA, Sahni G, Mandawat A, Mahmoudi M, Ganatra S, Ederhy S, Zatarain-Nicolas E, Groarke JD, Tocchetti CG, Lyon AR, Thavendiranathan P, Cohen JV, Reynolds KL, Fradley MG, Neilan TG

PMID: 32539614 [PubMed - in process]

13:30

pubmed: tutte cardiotoxicity...

Predictors of anthracycline-induced cardiotoxicity in a retro-prolective cohort of children surviving cancer.

Gac Med Mex. 2020;156(3):217-223

Authors: Rivas-Ruiz R, Ureña-Wong K, Castelán-Martínez OD, Betanzos-Cabrera Y, Lazo-Cárdenas C, Ramírez-Portillo C, López-Aguilar E