ABSTRACT

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear.

PMID:37812888 | DOI:10.1016/j.biopha.2023.115651

03:03

PubMed articles on: Cardio-Oncology

Cardiac Safety of Pegylated Liposomal Doxorubicin After Conventional Doxorubicin Exposure in Patients With Sarcoma and Breast Cancer

Cureus. 2023 Sep 7;15(9):e44837. doi: 10.7759/cureus.44837. eCollection 2023 Sep.

ABSTRACT

BACKGROUND: Lifetime cumulative doses of conventional doxorubicin (>450 mg/m2) are associated with dose-dependent cardiotoxicity. In sarcoma and breast cancer, conventional doxorubicin is often utilized in the adjuvant setting, whereas pegylated liposomal doxorubicin (PLD) is typically reserved for recurrent and metastatic disease. PLD is believed to be associated with reduced cardiotoxicity compared to conventional doxorubicin. Limited data exists evaluating the cardiotoxicity associated with PLD treatment after conventional doxorubicin, especially when doxorubicin lifetime doses approach the established cumulative total lifetime dose of 450-550 mg/m2. This study aims to further qualify the cardiac safety of PLD use in patients who have had prior exposure to conventional doxorubicin.

METHODS: This was a single-center, observational, retrospective cohort study conducted in patients ≥18 years with sarcoma or breast cancer who were exposed to conventional doxorubicin from an earlier line of treatment before PLD between January 2010 to May 2022. Patients were evaluated for the presence of cardiac toxicity at any point in their treatment course. Cardiac toxicity was defined as ≥ 10% decrease in left ventricle ejection fraction (LVEF) or a new diagnosis of heart failure within six months after PLD cessation. The time interval between the last conventional doxorubicin exposure and PLD initiation and the time interval between PLD initiation and LVEF monitoring were also analyzed.

RESULTS: 494 patients were screened, and 50 met inclusion criteria: eight with sarcoma and 42 with breast cancer. The median lifetime cumulative conventional doxorubicin dose in patients with sarcoma was 450 mg/m2 with a maximum dose of 825 mg/m2 and 240 mg/m2 with a maximum dose of 300 mg/m2 in breast cancer patients. The median lifetime cumulative PLD dose was 105 mg/m2 (range: 35-150 mg/m2) in the sarcoma group and 105 mg/m2 (range: 35-510 mg/m2) in the breast cancer group. A decrease of ≥ 10% in LVEF was not observed in the sarcoma group. Patients with breast cancer had available LVEF data on PLD, and three of these patients experienced ≥ 10% in LVEF drop, with one of these patients diagnosed with heart failure. The average cumulative dose of PLD administered in patients with > 10% decrease in LVEF was 177 mg/m2 and had an average of 3.5 cycles. Five sarcoma patients initiated PLD treatment within two years after conventional doxorubicin exposure, while most breast patients initiated PLD treatment at least 10 years following conventional doxorubicin exposure. The average time from PLD initiation to first and second available LVEF monitoring was one and five months in the sarcoma group and three and eight months in the breast cancer group, respectively.

CONCLUSION: PLD administration in patients with prior exposure to conventional doxorubicin appears to be safe, with limited cardiotoxicity in patients with sarcoma and breast cancer. Future research is needed to determine if and how often routine cardiac monitoring is needed for patients on PLD without existing cardiac risk.

PMID:37809186 | PMC:PMC10559758 | DOI:10.7759/cureus.44837

03:03

PubMed articles on: Cardio-Oncology

Papillary Adenocarcinoma: A Rare Subtype of Lung Adenocarcinoma

Cureus. 2023 Sep 7;15(9):e44838. doi: 10.7759/cureus.44838. eCollection 2023 Sep.

ABSTRACT

Papillary adenocarcinoma (PA) of the lung is a specific form of lung cancer characterized by papillary structures in tumor cells. This type of cancer is relatively rare and has distinct pathological and radiological features that differentiate it from other types of lung adenocarcinomas. Determining the specific subtype of adenocarcinoma is a crucial factor in the choice of chemotherapy treatment. Detecting PA is fundamental, as it has both prognostic and therapeutic implications for patients with lung carcinoma. In this paper, we discuss two cases of young patients diagnosed with PA of the lung. The cases we present are particularly intriguing due to the relatively young age of the patients.

PMID:37809161 | PMC:PMC10560075 | DOI:10.7759/cureus.44838

03:03

PubMed articles on: Cardio-Oncology

Deep learning-assisted high-content screening identifies isoliquiritigenin as an inhibitor of DNA double-strand breaks for preventing doxorubicin-induced cardiotoxicity

Biol Direct. 2023 Oct 9;18(1):63. doi: 10.1186/s13062-023-00412-7.

ABSTRACT

BACKGROUND: Anthracyclines including doxorubicin are essential components of many cancer chemotherapy regimens, but their cardiotoxicity severely limits their use. New strategies for treating anthracycline-induced cardiotoxicity (AIC) are still needed. Anthracycline-induced DNA double-strand break (DSB) is the major cause of its cardiotoxicity. However, DSB-based drug screening for AIC has not been performed possibly due to the limited throughput of common assays for detecting DSB. To discover new therapeutic candidates for AIC, here we established a method to rapidly visualize and accurately evaluate the intranuclear anthracycline-induced DSB, and performed a screening for DSB inhibitors.

RESULTS: First, we constructed a cardiomyocyte cell line stably expressing EGFP-53BP1, in which the formation of EGFP-53BP1 foci faithfully marked the doxorubicin-induced DSB, providing a faster and visible approach to detecting DSB. To quantify the DSB, we used a deep learning-based image analysis method, which showed the better ability to distinguish different cell populations undergoing different treatments of doxorubicin or reference compounds, compared with the traditional threshold-based method. Subsequently, we applied the deep learning-assisted high-content screening method to 315 compounds and found three compounds (kaempferol, kaempferide, and isoliquiritigenin) that exert cardioprotective effects in vitro. Among them, the protective effect of isoliquiritigenin is accompanied by the up-regulation of HO-1, down-regulation of peroxynitrite and topo II, and the alleviation of doxorubicin-induced DSB and apoptosis. The results of animal experiments also showed that isoliquiritigenin maintained the myocardial tissue structure and cardiac function in vivo. Moreover, isoliquiritigenin did not affect the killing of HeLa and MDA-MB-436 cancer cells by doxorubicin and thus has the potential to be a lead compound to exert cardioprotective effects without affecting the antitumor effect of doxorubicin.

CONCLUSIONS: Our findings provided a new method for the drug discovery for AIC, which combines phenotypic screening with artificial intelligence. The results suggested that isoliquiritigenin as an inhibitor of DSB may be a promising drug candidate for AIC.

PMID:37807075 | PMC:PMC10561451 | DOI:10.1186/s13062-023-00412-7

03:03

PubMed articles on: Cardio-Oncology

Alterations in Left Atrial Strain in Breast Cancer Patients Immediately Post Anthracycline Exposure

Heart Lung Circ. 2023 Oct 6:S1443-9506(23)04291-9. doi: 10.1016/j.hlc.2023.06.864. Online ahead of print.

ABSTRACT

AIMS: With improved diagnosis and treatments, a greater percentage of breast cancer patients are achieving long-term survival. Consequently, long-term cardiotoxicity secondary to chemotherapy has become more prevalent, warranting improved cardiac surveillance. We evaluated changes in left atrial (LA) strain in breast cancer patients immediately post anthracycline (AC) therapy to assess its utility as a marker of diastolic dysfunction.

METHODS: This was a prospective cohort study of 128 consecutive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who underwent transthoracic echocardiography prior to and immediately post AC treatment. Traditional left ventricular (LV) systolic and diastolic parameters and LA volumes were evaluated; additionally, LV global longitudinal strain (LV GLS) and LA phasic strain were measured.

RESULTS: All patients had normal LV ejection fraction (>53%) post AC, though LV GLS was significantly reduced. Peak E and é velocities were reduced post AC, with no change in LA volumes. LA reservoir strain (LASRES 34.8% vs 31.5%, p<0.001)CD 17.2% vs 14.4%, p<0.001)RES from baseline) (32%) compared to alteration in systolic function (≥15% reduction in LV GLS) (23%).

CONCLUSIONS: LA strain is a promising marker of early diastolic dysfunction. We demonstrate its potential utility in surveillance of breast cancer patients treated with AC.

PMID:37806911 | DOI:10.1016/j.hlc.2023.06.864

03:03

PubMed articles on: Cardio-Oncology

Inhibiting mir-34a-5p regulates doxorubicin-induced autophagy disorder and alleviates myocardial pyroptosis by targeting Sirt3-AMPK pathway

Biomed Pharmacother. 2023 Oct 6;168:115654. doi: 10.1016/j.biopha.2023.115654. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) is a commonly used chemotherapy drug widely applied in various cancers such as breast cancer, leukemia, and sarcomas. However, its usage is limited by cardiotoxicity. Additionally, the cardiac toxicity of DOX accumulates with dose and duration, making it imperative to identify therapeutic targets for DOX-induced cardiomyopathy (DIC). It has been reported that miRNAs are involved in the progression of DIC. Mir-34a-5p has been identified as an early diagnostic marker for DIC. While studies have shown the involvement of mir-34a-5p in DIC apoptosis, it has not been validated in animal models, nor has the potential improvement of DIC by inhibiting mir-34a-5p been confirmed. Autophagy and pyroptosis are key factors in the development of DIC and can serve as therapeutic targets for its treatment. In this study, we found that mir-34a-5p was upregulated in the heart after DOX treatment and that the inhibition of mir-34-5p reduced autophagy and pyroptosis in DIC. We also found that the inhibition of mir-34a-5p inhibited pyroptosis by regulating autophagy and reducing mitochondrial reactive oxygen species. Moreover, we identified Sirtuin3 (Sirt3) as a target gene of mir-34a-5p using a double-luciferase reporter assay. overexpression Sirt3 reduced pyroptosis by alleviating autophagy. Our research findings suggest that inhibiting mir-34a-5p has a beneficial role in alleviating autophagy and pyroptosis in DIC. This provides therapeutic prospects for treating DIC.

PMID:37806095 | DOI:10.1016/j.biopha.2023.115654

03:03

PubMed articles on: Cardio-Oncology

Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer

Cardiovasc Toxicol. 2023 Oct 7. doi: 10.1007/s12012-023-09807-4. Online ahead of print.

ABSTRACT

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model's net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan-Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram's net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

PMID:37804372 | DOI:10.1007/s12012-023-09807-4

03:03

PubMed articles on: Cardio-Oncology

Outcomes of patients with active cancers and pre-existing cardiovascular diseases infected with SARS-CoV-2

Cardiooncology. 2023 Oct 6;9(1):36. doi: 10.1186/s40959-023-00187-w.

ABSTRACT

OBJECTIVE: To determine the impact of acute SARS-CoV-2 infection on patient with concomitant active cancer and CVD.

METHODS: The researchers extracted and analyzed data from the National COVID Cohort Collaborative (N3C) database between January 1, 2020, and July 22, 2022. They included only patients with acute SARS-CoV-2 infection, defined as a positive test by PCR 21 days before and 5 days after the day of index hospitalization. Active cancers were defined as last cancer drug administered within 30 days of index admission. The "Cardioonc" group consisted of patients with CVD and active cancers. The cohort was divided into four groups: (1) CVD (-), (2) CVD ( +), (3) Cardioonc (-), and (4) Cardioonc ( +), where (-) or ( +) denotes acute SARS-CoV-2 infection status. The primary outcome of the study was major adverse cardiovascular events (MACE), including acute stroke, acute heart failure, myocardial infarction, or all-cause mortality. The researchers analyzed the outcomes by different phases of the pandemic and performed competing-risk analysis for other MACE components and death as a competing event.

RESULTS: The study analyzed 418,306 patients, of which 74%, 10%, 15.7%, and 0.3% had CVD (-), CVD ( +), Cardioonc (-), and Cardioonc ( +), respectively. The Cardioonc ( +) group had the highest MACE events in all four phases of the pandemic. Compared to CVD (-), the Cardioonc ( +) group had an odds ratio of 1.66 for MACE. However, during the Omicron era, there was a statistically significant increased risk for MACE in the Cardioonc ( +) group compared to CVD (-). Competing risk analysis showed that all-cause mortality was significantly higher in the Cardioonc ( +) group and limited other MACE events from occurring. When the researchers identified specific cancer types, patients with colon cancer had higher MACE.

CONCLUSION: In conclusion, the study found that patients with both CVD and active cancer suffered relatively worse outcomes when they had acute SARS-CoV-2 infection during early and alpha surges in the United States. These findings highlight the need for improved management strategies and further research to better understand the impact of the virus on vulnerable populations during the COVID-19 pandemic.

PMID:37803479 | PMC:PMC10557272 | DOI:10.1186/s40959-023-00187-w

03:04

PubMed articles on: Cardio-Oncology

Editorial: Cancer treatment-related cardiovascular disease - real world data in cardio-oncology

Front Oncol. 2023 Sep 20;13:1277042. doi: 10.3389/fonc.2023.1277042. eCollection 2023.

NO ABSTRACT

PMID:37799461 | PMC:PMC10548460 | DOI:10.3389/fonc.2023.1277042

03:04

PubMed articles on: Cardio-Oncology

Clinical Utility and Prognostic Value of Coronary Computed Tomography Angiography in Patients With Cancer

Am J Cardiol. 2023 Oct 3;207:448-454. doi: 10.1016/j.amjcard.2023.08.121. Online ahead of print.

ABSTRACT

There is growing interest in the role of coronary computed tomography angiography (CTA) in cardio-oncology. However, there is a paucity of real-world experience and outcome data for patients with cancer. This study sought to determine the clinical utility and prognostic value of coronary CTA in patients with cancer. In this prospective, single-center study, we recruited patients with cancer who underwent coronary CTA. Coronary artery disease (CAD) extent was classified as normal, nonobstructive (1% to 49% stenosis), and potentially obstructive (≥50% stenosis). Patients were followed up for a median of 9 months (interquartile range 3 to 30 months) for cancer-related deaths and major adverse cardiovascular events (MACEs) defined as nonfatal myocardial infarction, urgent unplanned revascularization, or cardiovascular death. The mean age of patients (n = 113) was 61 ± 12 years, and 68 were female (60%). The most common underlying cancers were breast (29%) and lymphoma (13%). A total of 25 patients had potentially obstructive CAD, most commonly of the left anterior descending artery. After coronary CTA, 88% statin-naive patients with potentially obstructive CAD were initiated on statin therapy. A total of 28/32 patients who were taking fluoropyrimidine chemotherapy (5-fluorouracil or capecitabine) continued therapy, of whom none had MACEs. Overall, there were no episodes of MACEs in this cohort and 11% had cancer-related deaths. Coronary CTA has an important role in the clinical decision-making in patients with cancer to detect CAD, initiate primary preventative therapy, and guide coronary revascularization. No MACEs occurred. Using this coronary CTA-guided approach, preventative therapy was initiated, and most patients continued prognostically important cancer therapy.

PMID:37797552 | DOI:10.1016/j.amjcard.2023.08.121

03:04

PubMed articles on: Cardio-Oncology

Advances in Screening for Radiation-Associated Cardiotoxicity in Cancer Patients

Curr Cardiol Rep. 2023 Oct 5. doi: 10.1007/s11886-023-01971-x. Online ahead of print.