ABSTRACT

[This retracts the article DOI: 10.1155/2022/7963146.].

PMID:37475923 | PMC:PMC10356376 | DOI:10.1155/2023/9783196

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PubMed articles on: Cardio-Oncology

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer

Zhongguo Zhong Yao Za Zhi. 2023 Jul;48(13):3472-3484. doi: 10.19540/j.cnki.cjcmm.20230410.301.

ABSTRACT

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01).<0.05).<0.05),

PMID:37474984 | DOI:10.19540/j.cnki.cjcmm.20230410.301

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PubMed articles on: Cardio-Oncology

Nuclear translocation of mitochondrial dehydrogenases as an adaptive cardioprotective mechanism

Nat Commun. 2023 Jul 19;14(1):4360. doi: 10.1038/s41467-023-40084-5.

ABSTRACT

Chemotherapy-induced cardiac damage remains a leading cause of death amongst cancer survivors. Anthracycline-induced cardiotoxicity is mediated by severe mitochondrial injury, but little is known about the mechanisms by which cardiomyocytes adaptively respond to the injury. We observed the translocation of selected mitochondrial tricarboxylic acid (TCA) cycle dehydrogenases to the nucleus as an adaptive stress response to anthracycline-cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes and in vivo. The expression of nuclear-targeted mitochondrial dehydrogenases shifts the nuclear metabolic milieu to maintain their function both in vitro and in vivo. This protective effect is mediated by two parallel pathways: metabolite-induced chromatin accessibility and AMP-kinase (AMPK) signaling. The extent of chemotherapy-induced cardiac damage thus reflects a balance between mitochondrial injury and the protective response initiated by the nuclear pool of mitochondrial dehydrogenases. Our study identifies nuclear translocation of mitochondrial dehydrogenases as an endogenous adaptive mechanism that can be leveraged to attenuate cardiomyocyte injury.

PMID:37468519 | PMC:PMC10356764 | DOI:10.1038/s41467-023-40084-5

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PubMed articles on: Cardio-Oncology

Tales from the future - Nuclear cardio-oncology, from prediction to diagnosis and monitoring

Eur Heart J Cardiovasc Imaging. 2023 Jul 19:jead168. doi: 10.1093/ehjci/jead168. Online ahead of print.

ABSTRACT

Cancer and cardiovascular disease often share common risk factors, and patients with cardiovascular disease who develop cancer are at high risk of experiencing major adverse cardiac events. Additionally, cancer treatment can induce short- and long-term adverse cardiovascular events. Given the improvement in oncological patients' prognosis, the burden in this vulnerable population is slowly shifting towards increased cardiovascular mortality. Consequently, the field of cardio-oncology is steadily expanding, prompting the need for new markers to stratify and monitor the cardiovascular risk in oncological patients before, during, and after the completion of treatment. Advanced noninvasive cardiac imaging has raised great interest in the early detection of cardiovascular diseases and cardiotoxicity in oncological patients. Nuclear medicine has long been a pivotal exam to robustly assess and monitor the cardiac function of patients undergoing potentially cardiotoxic chemotherapies. In addition, recent radiotracers have shown great interest in the early detection of cancer treatment-related cardiotoxicity. In this review, we summarize the current and emerging nuclear cardiology tools that can help identify cardiotoxicity and assess the cardiovascular risk in patients undergoing cancer treatments, and discuss the specific role of nuclear cardiology alongside other noninvasive imaging techniques.

PMID:37467476 | DOI:10.1093/ehjci/jead168

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PubMed articles on: Cardio-Oncology

Protocol: Can coronary artery calcium score identified on thoracic planning CT scans be used and actioned to identify cancer survivors at high risk of cardiac events: A feasibility study in cancer survivors undergoing radiotherapy in Australia

BMJ Open. 2023 Jul 18;13(7):e072376. doi: 10.1136/bmjopen-2023-072376.

ABSTRACT

INTRODUCTION: A coronary artery calcium (CAC) CT scan can identify calcified plaque and predict risk of future cardiac events. Cancer survivors undergoing thoracic radiotherapy routinely undergo a planning CT scan, which presents a unique opportunity to use already obtained medical imaging to identify those at the highest risk of cardiac events. While radiation therapy is an important modality for many cancer treatments, radiation dose to the heart in thoracic radiotherapy leads to cardiotoxicity and may accelerate pre-existing atherosclerosis. The primary aims of this study are to investigate the feasibility of using CAC scores calculated on thoracic radiotherapy planning CT scans to identify a subset of cancer survivors at an increased risk of future cardiac events, and to establish and evaluate a referral pathway for assessment and management in a cardio-oncology clinic. An optional substudy aims to investigate using abdominal aortic calcification (AAC) as a practical, low-radiation alternative to CAC to evaluate and monitor vascular health.

METHODS AND ANALYSIS: This is an observational, prospective study in a minimum of 100 cancer survivors commencing radiotherapy. Participants will have CAC scored from thoracic radiotherapy planning CT scans. Those identified as high risk (CAC score>0) will be referred to a cardio-oncology clinic. Feasibility, determined by adherence to the recommended pathway, and impact on quality of life and anxiety measured via questionnaire, will be assessed. Participants in Western Australia will be invited to participate in a 12-month observational pilot substudy, investigating lifestyle behaviours and the use of a dual-energy X-ray absorptiometry machine to measure musculoskeletal health and AAC.

ETHICS AND DISSEMINATION: Ethics approval has been obtained from St Vincent's Hospital, Sydney (Project number 2021/ETH11847), GenesisCare and Edith Cowan University (2022-03326-DALLAVIA). Study results will be reported in peer-reviewed academic journals, at scientific conferences, and at clinical forums, irrespective of the results observed.

TRIAL REGISTRATION NUMBER: ACTRN12621001343897.

PMID:37463809 | PMC:PMC10357636 | DOI:10.1136/bmjopen-2023-072376

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PubMed articles on: Cardio-Oncology

Mediators of Black-White inequities in cardiovascular mortality among survivors of 18 cancers in the USA

Int J Epidemiol. 2023 Jul 20:dyad097. doi: 10.1093/ije/dyad097. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to quantify Black-White inequities in cardiovascular disease (CVD) mortality among US survivors of 18 adult-onset cancers and the extent to which these inequities are explained by differences in socio-economic and clinical factors.

METHODS: Survivors of cancers diagnosed at ages 20-64 years during 2007-16 were identified from 17 Surveillance, Epidemiology and End Results registries. Associations between race and CVD mortality were examined using proportional hazards models. Mediation analyses were performed to quantify the contributions of potential mediators, including socio-economic [health insurance, neighbourhood socio-economic status (nSES), rurality] and clinical (stage, surgery, chemotherapy, radiotherapy) factors.

RESULTS: Among 904 995 survivors, 10 701 CVD deaths occurred (median follow-up, 43 months). Black survivors were more likely than White survivors to die from CVD for all 18 cancers with hazard ratios ranging from 1.30 (95% CI = 1.15-1.47) for lung cancer to 4.04 for brain cancer (95% CI = 2.79-5.83). The total percentage mediations (indirect effects) ranged from 24.8% for brain (95% CI=-5.2-59.6%) to 99.8% for lung (95% CI = 61.0-167%) cancers. Neighbourhood SES was identified as the strongest mediator for 14 cancers with percentage mediations varying from 25.0% for kidney cancer (95% CI = 14.1-36.3%) to 63.5% for lung cancer (95% CI = 36.5-108.7%). Insurance ranked second for 12 cancers with percentage mediations ranging from 12.3% for leukaemia (95% CI = 0.7-46.7%) to 31.3% for thyroid cancer (95% CI = 10.4-82.7%).

CONCLUSIONS: Insurance and nSES explained substantial proportions of the excess CVD mortality among Black survivors. Mitigating the effects of unequal access to care and differing opportunities for healthy living among neighbourhoods could substantially reduce racial inequities in CVD mortality among cancer survivors.

PMID:37471575 | DOI:10.1093/ije/dyad097

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PubMed articles on: Cardio-Oncology

Cisplatin-based combination therapy for cancer

J Cancer Res Ther. 2023 Jul-Sep;19(3):530-536. doi: 10.4103/jcrt.jcrt_792_22.

ABSTRACT

Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug therapy to reduce the side effects in cancer therapy.

PMID:37470570 | DOI:10.4103/jcrt.jcrt_792_22

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Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients

Ann Hematol. 2023 Jul 21. doi: 10.1007/s00277-023-05369-1. Online ahead of print.

ABSTRACT

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

PMID:37479891 | DOI:10.1007/s00277-023-05369-1

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PubMed articles on: Cancer & VTE/PE

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE

J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.

OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.

RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.

PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007

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PubMed articles on: Cancer & VTE/PE

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice

Curr Res Transl Med. 2023 Jul 13;71(3):103405. doi: 10.1016/j.retram.2023.103405. Online ahead of print.