Abstract
Doxorubicin (DOX) is an anthracycline widely used in cancer therapy and in particular in breast cancer treatment. The treatment with DOX appears successful, but it is limited by a severe cardiotoxicity. This work evaluated the in vitro and in vivo anticancer effect of a new formulation of β-cyclodextrin nanosponges containing DOX (BNS-DOX). The BNS-DOX effectiveness was evaluated in human and mouse breast cancer cell lines in vitro in terms of effect on cell growth, cell cycle distribution, and apoptosis induction; and in vivo in BALB-neuT mice developing spontaneous breast cancer in terms of biodistribution, cancer growth inhibition, and heart toxicity. BNS-DOX significantly inhibited cancer cell proliferation, through the induction of apoptosis, with higher efficiency than free DOX. The breast cancer growth in BALB-neuT mice was inhibited by 60% by a BNS-DOX dose five times lower than the DOX therapeutic dose, with substantial reduction of tumor neoangiogenesis and lymphangiogenesis. Biodistribution after BNS-DOX treatment revealed a high accumulation of DOX in the tumor site and a low accumulation in the hearts of mice. Results indicated that use of BNS may be an efficient strategy to deliver DOX in the treatment of breast cancer, since it improves the anti-cancer effectiveness and reduces cardiotoxicity.
PMID: 31936526 [PubMed]
17 January 2020
15:14
Cardiotoxicity News
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
15:14
In reply to this message
pubmed: tutte cardiotoxicity...
Helping the cardio-oncologist: from real life to guidelines.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
Helping the cardio-oncologist: from real life to guidelines.
Semin Oncol. 2019 12;46(6):433-436
Authors: Armenian SH, Jurczak W, Carver JR, Gennari A, Minotti G, Ewer MS
Abstract
Guidelines for the diagnosis, management, and surveillance of cancer patients have evolved with the single goal of improving patient care based on established data when available, or in the absence of firm data, on the standard practices of those with broad experience in actual hands-on patient care. Two initiatives intended to disseminate information to cardio-oncologists, were discussed in this session: the first, from the American Society of Clinical Oncology was focused on available data and the confidence level of that data; the second, from The European Society of Cardiology was a position paper. Interestingly, notwithstanding the somewhat different focus, there is considerable agreement between these two initiatives. Nevertheless, guidelines my not be applicable to all afflicted patients, and may raise questions as to when deviations from published standards should be considered. Such deviations may result in allegations of failure to meet standards of care or legal liability.
PMID: 31784041 [PubMed - in process]
15:14
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
15:14
In reply to this message
pubmed: tutte cardiotoxicity...
Old and new directions of Cardio-Oncology.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
Old and new directions of Cardio-Oncology.
Semin Oncol. 2019 12;46(6):395-396
Authors: Ewer MS, Carver JR, Minotti G
PMID: 31767271 [PubMed - in process]
15:14
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
15:15
In reply to this message
pubmed: tutte cardiotoxicity...
Cardio-oncology in clinical studies and real life.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
Cardio-oncology in clinical studies and real life.
Semin Oncol. 2019 12;46(6):421-425
Authors: Dent SF, Suter TM, López-Fernández T, Opolski G, Menna P, Minotti G
Abstract
Session V of the Colloquium was chaired by Professors Teresa López-Fernández of Spain and Grzegorz Opolski of Poland. The 3 speakers addressed cardio-oncology issues as they relate to both clinical studies and real life situations. Professor Susan Dent discussed cardio-oncology networks for patients, emphasizing the importance of establishing a framework where the expertise of the cardiology consultant can supplement and reinforce the goals of optimal cancer therapy. Professor Thomas Suter moved the discussion further, sharing his insight into cardiac monitoring in clinical trials, emphasizing the lack of uniform criteria and lack of consensus regarding reversibility of cardiac events and long-term implications of modest declines in systolic function frequently found in clinical trials for which long-term follow-up may not be a component of the trial. Professor Giorgio Minotti added important considerations to the discussion of clinical trials. He emphasized that the usual reporting of cardiac systolic function omits important diastolic dysfunction data generated but often ignored during the routine cardiac exams. The inclusion of cardiac biomarker changes would also help to broaden the perspective of cardiac effects and events seen in patients enrolled in clinical trials.
PMID: 31767270 [PubMed - in process]
15:15
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
15:15
In reply to this message
pubmed: tutte cardiotoxicity...
Mechanisms and clinical course of cardiovascular toxicity of cancer treatment II. Hematology☆.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
Mechanisms and clinical course of cardiovascular toxicity of cancer treatment II. Hematology☆.
Semin Oncol. 2019 12;46(6):403-407
Authors: Breccia M, Carver JR, Szmit S, Jurczak W, Salvatorelli E, Minotti G
Abstract
Session II of the Second International Colloquium on Cardio-Oncology, chaired by Dr Breccia (Rome, Italy) and Dr Jurczak (Krakòw, Poland), focused on mechanisms and clinical course of cardiovascular toxicity of cancer treatment. Whereas the venerable anthracyclines keep challenging patients and clinicians with risk of left ventricular dysfunction and heart failure, other newer drugs cause substantially different clinical phenotypes of cardiovascular toxicity. In particular, Session II not only focused on arterial thrombosis and venous thromboembolism, but also hypertension or cardiomyopathy or atrial fibrillation induced by many otherwise life-saving drugs. Dr Breccia (Rome, Italy) reviewed incidence, mechanisms, risk factors, and principles for prevention of cardiovascular events induced by tyrosine kinase inhibitors of hematologic interest, such as those used to treat chronic myeloid leukemia. Dr Carver (Philadelphia) reviewed the incidence, predisposing factors, and principles for proactive management of cardiovascular events in patients treated by conventional chemotherapy or new drugs for treatment of multiple myeloma. Dr Szmit (Warsaw, Poland) discussed on how coagulation disorders should be classified according to patient- or drug-related factors and how they should be diagnosed and treated in patients with solid or hematologic tumors. Dr Minotti (Rome. Italy) illustrated some potential pitfalls of accelerated drug development and approval and their possible impact on clinical incidence of cardiovascular events induced by tyrosine kinase inhibitors of hematologic interest. Session II therefore offered a broad perspective of the risk-benefit ratio of new drugs that are plagued with concerns about cardiovascular events.
PMID: 31748121 [PubMed - in process]
20 January 2020
12:37
Cardiotoxicity News
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
12:37
In reply to this message
pubmed: tutte cardiotoxicity...
Carbonyl reductase 1 plays a significant role in converting doxorubicin to cardiotoxic doxorubicinol in mouse liver, but the majority of the doxorubicinol-forming activity remains unidentified.
Carbonyl reductase 1 plays a significant role in converting doxorubicin to cardiotoxic doxorubicinol in mouse liver, but the majority of the doxorubicinol-forming activity remains unidentified.
Drug Metab Dispos. 2020 Jan 18;:
Authors: Breysse DH, Boone RM, Long CM, Merrill ME, Schaupp CM, White CC, Kavanagh TJ, Schmidt EE, Merrill GF
Abstract
Doxorubicin is a widely used cancer therapeutic, but its effectiveness is limited by cardiotoxic side effects. Evidence suggests cardiotoxicity is due not to doxorubicin, but rather its metabolite, doxorubicinol. Identification of the enzymes responsible for doxorubicinol formation is important in developing strategies to prevent cardiotoxicity. In this study, the contributions of three murine candidate enzymes to doxorubicinol formation were evaluated: carbonyl reductase 1 (Cbr1), carbonyl reductase 3 (Cbr3), and thioredoxin reductase 1 (Tr1). Analyses with purified proteins revealed that all three enzymes catalyzed doxorubicin-dependent NADPH oxidation, but only Cbr1 and Cbr3 catalyzed doxorubicinol formation. Doxorubicin-dependent NADPH oxidation by Tr1 was likely due to redox cycling. Subcellular fractionation results showed that doxorubicin-dependent redox cycling activity was primarily microsomal, whereas doxorubicinol-forming activity was exclusively cytosolic, as were all three enzymes. An immunoclearing approach was used to assess the contributions of the three enzymes to doxorubicinol formation in the complex milieu of the cytosol. Immunoclearing Cbr1 eliminated 25% of the total doxorubicinol-forming activity in cytosol, but immunoclearing Cbr3 had no effect, even in Tr1 null livers that overexpressed Cbr3. The immunoclearing results constituted strong evidence that Cbr1 contributed to doxorubicinol formation in mouse liver, but that enzymes other than Cbr1 also played a role, a conclusion supported by ammonium sulfate fractionation results, which showed that doxorubicinol-forming activity was found in fractions that contained little Cbr1. In conclusion, the results show that Cbr1 accounts for 25% of the doxorubicinol-forming activity in mouse liver cytosol but that the majority of the doxorubicinol-forming activity remains unidentified. SIGNIFICANCE STATEMENT: Earlier genetic and drug inhibition results suggested Cbr1 plays a dominant role in converting chemotherapeutic doxorubicin to cardiotoxic doxorubicinol, but a new immunoclearing approach described herein shows that Cbr1 accounts for only 25% of the doxorubicinol-forming activity in mouse liver cytosol, that two other candidate enzymes Cbr3 and Tr1 play no role, and that the majority of the activity remains unidentified. The results suggest that targeting Cbr1 is necessary but not sufficient to eliminate doxorubicinol-associated cardiotoxicity; identification and targeting of the additional doxorubicinol-forming activity is an important next challenge.
PMID: 31955137 [PubMed - as supplied by publisher]
21 January 2020
13:22
Cardiotoxicity News
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
13:22
Comments
Post a Comment
اكتب تعليق حول الموضوع