ABSTRACT

Considering the resistance and toxicity of traditional chemotherapeutic drugs, seeking potential candidate for treating breast cancer effectively is a clinical problem that should be solved urgently. Natural products have attracted extensive attention, owing to their multi-target advantages and low toxicity. In the current study, the effects of XK-81, a novel bromophenol compound extracted from Leathesia nana, on breast cancer, and its underlying mechanisms, were explored. Firstly, data from in vitro experiments indicated that 4T-1, one of common mouse breast cancer cell lines, was a XK-81-susceptible cell line, and ferroptosis was the major death manner in response to XK-81 treatment, which was evidenced by increasing intracellular Fe2+ and ROS level with condensed mitochondrial membrane densities, as well as decreasing the protein expressions of SLC7A11 and GPX4. In vivo, XK-81 suppressed the growth of 4T-1 breast-tumor in both BALB/C mice and zebrafish. Obviously, XK-81 decreased the protein expression of SLC7A11 and GPX4 in tumor tissues, hinting at the occurrence of ferroptosis. Moreover, XK-81 increased CD8+ T cells and NK cells numbers and regulated M1/M2 macrophage ratio in tumor tissues, indicating XK-81's immunotherapeutic effect. Additionally, the secretions of immune-related cytokines, including TNF-α, IL-1β, and IL-12, were elevated with XK-81 stimulation in RAW 264.7 cells. Intriguingly, compared with doxorubicin-induced heart damage, XK-81 demonstrated the therapeutic advantage of little cardiotoxicity on the heart. XK-81 demonstrated potential antitumor advantage by both directly inducing ferroptosis-mediated death of tumor cells and immunization.

PMID:37513222 | PMC:PMC10385854 | DOI:10.3390/molecules28145349

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PubMed articles on: Cardio-Oncology

Role of hypoxia inducible factor/vascular endothelial growth factor/endothelial nitric oxide synthase signaling pathway in mediating the cardioprotective effect of dapagliflozin in cyclophosphamide-induced cardiotoxicity

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PubMed articles on: Cardio-Oncology

Neopetroside-B alleviates doxorubicin-induced cardiotoxicity via mitochondrial protection

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PubMed articles on: Cardio-Oncology

Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming

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PubMed articles on: Cardio-Oncology

Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe

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PubMed articles on: Cardio-Oncology

Cardio-oncology today: digest of the first European clinical guidelines (2022)

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PubMed articles on: Cardio-Oncology

Current Cardioprotective Strategies for the Prevention of Radiation-Induced Cardiotoxicity in Left-Sided Breast Cancer Patients

J Pers Med. 2023 Jun 24;13(7):1038. doi: 10.3390/jpm13071038.

ABSTRACT

BACKGROUND: Breast cancer (BC) is the most common malignancy in females, accounting for the majority of cancer-related deaths worldwide. There is well-established understanding about the effective role of radiotherapy (RT) in BC therapeutic strategies, offering a better local-regional control, prolonged survival, and improved quality of life for patients. However, it has been proven that conventional RT modalities, especially in left-sided BC cases, are unable to avoid the administration of high RT doses to the heart, thus resulting in cardiotoxicity and promoting long-term cardiovascular diseases (CVD). Recent radiotherapeutic techniques, characterized by dosimetric dose restrictions, target volume revision/modifications, an increased awareness of risk factors, and consistent follow-ups, have created an advantageous context for a significant decrease inpost-RT CVD incidence.

AIM: This review presents the fundamental role of current cardioprotective strategies in the prevention of cardiotoxic effects in left-BCRT.

MATERIAL AND METHODS: A literature search was conducted up to January 2023 using the Cochrane Central Register of Controlled Trials and PubMed Central databases. Our review refers to new radiotherapeutic techniques carried out on patients after BC surgery. Specifically, a dose evaluation of the heart and left anterior descending coronary artery (LADCA) was pointed out for all the included studies, depending on the implemented RT modality, bed positioning, and internal mammary lymph nodes radiation.

RESULTS: Several studies reporting improved heart sparing with new RT techniques in BC patients were searched. In addition to the RT modality, which definitely determines the feasibility of achieving lower doses for the organs at risk (OARs), better target coverage, dose conformity and homogeneity, and the patient's position, characteristics, and anatomy may also affect the evaluated RT dose to the whole heart and its substructures.

CONCLUSIONS: Modern BC RT techniques seem to enable the administration of lower doses to the OARs without compromising on the target coverage. The analysis of several anatomical parameters and the assessment of cardiac biomarkers potentiate the protective effect of these new irradiation modalities, providing a holistic approach to the radiation-associated risks of cardiac disease for BC patients. Despite technological advances, an inevitable cardiac radiation risk still exists, while adverse cardiac events may be observed even many years after RT. Studies with longer follow-ups are required in order to determine the effectiveness of modern breast RT techniques.

PMID:37511651 | PMC:PMC10381791 | DOI:10.3390/jpm13071038

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PubMed articles on: Cancer & VTE/PE

A novel risk prediction score for clinically significant bleeding in patients anticoagulated for venous thromboembolism with active cancer

Thromb Haemost. 2023 Aug 1. doi: 10.1055/a-2145-7238. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction.

METHODS: UK Clinical Practice Research Datalink data (2008-2020) was used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding, and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H). A scoring scheme was developed from subdistribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation.

RESULTS: 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds and 376 CRNMB-H were identified after adjudicated review in 4914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding were cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract. Overall C-statistic for significant bleeding was 0.70, and 0.76 and 0.67 for major bleeding and for CRNMB-H, respectively.

CONCLUSIONS: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

PMID:37527782 | DOI:10.1055/a-2145-7238

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PubMed articles on: Cancer & VTE/PE

Intravascular Tumor Extension and Pulmonary Tumor Embolism in Children With Solid Malignancies: Is There a Role for Inferior Vena Cava Filters?

J Pediatr Hematol Oncol. 2023 Jul 27. doi: 10.1097/MPH.0000000000002731. Online ahead of print.

ABSTRACT

Intravascular tumor extension is an uncommon complication of solid malignancies that, when present in the inferior vena cava (IVC), can result in fatal pulmonary tumor embolism. Currently, neoadjuvant chemotherapy and surgery are the mainstays of treatment; however, there are no consensus guidelines for management. We describe three cases of pediatric solid malignancies with associated IVC extension and pulmonary tumor embolism. We hypothesize that there is scope for IVC filter placement in such cases to mitigate the risk of fatal pulmonary tumor embolism.

PMID:37526419 | DOI:10.1097/MPH.0000000000002731

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PubMed articles on: Cancer & VTE/PE

Tissue factor positive microparticles as a biomarker for increased risk of breast cancer-associated thrombosis: a mini review

Curr Opin Hematol. 2023 Sep 1;30(5):180-185. doi: 10.1097/MOH.0000000000000774.

ABSTRACT

PURPOSE OF REVIEW: Cancer-associated thrombosis (CAT), such as venous thromboembolism (VTE), is a frequent complication in cancer patients, resulting in poor prognosis. Breast cancer is not highly thrombogenic but is highly prevalent, resulting in increased VTE cases. Many cancers express tissue factor (TF), a glycoprotein that triggers coagulation. The cancer cells were shown to express and release substantial amounts of TF-positive microparticles (MPTF), associated with a prothrombotic state. This narrative review evaluated the current use of the procoagulant MPTF as a biomarker for thrombosis risk in breast cancer.

RECENT FINDINGS: Tumors of epithelial origin with elevated TF expression have been associated with increased VTE incidence. Thus, studies have affirmed the use of MPTF biomarkers for VTE risk in many cancers. Patients with metastatic breast cancer and CAT were found to exhibit elevated procoagulant microparticles in vitro, due to TF expression. The silencing of TF was associated with decreased microparticle release in breast carcinoma cell lines, associated with decreased coagulation.

SUMMARY: CAT is a multifactorial condition, with several various underlying diseases. It is proposed that MPTF may be an effective biomarker for thrombosis risk in breast cancer patients but requires a more systemic evaluation utilizing standardized quantification methods.

PMID:37522480 | DOI:10.1097/MOH.0000000000000774

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PubMed articles on: Cancer & VTE/PE

Incidence and Factors Associated With Pulmonary Embolism After Upper Extremity Trauma: A Tertiary Hospital Experience in Turkey

Cureus. 2023 Jun 28;15(6):e41077. doi: 10.7759/cureus.41077. eCollection 2023 Jun.

ABSTRACT

Introduction Venous thromboembolism (VTE), particularly pulmonary embolism (PE), is the third highest cause of death in trauma patients who survive beyond the first day. Musculoskeletal surgery is associated with several complications, some of which may be life-threatening, including deep vein thrombosis (DVT) and PE. Objective This research aims to describe risk variables for VTE after upper extremity (UE) fracture at a single institution and estimate the incidence of PE following UE fracture. Methods The writers accessed the database via their respective universities using the International Standard Classification (ICD) codes. The medical files of patients aged 18 and older who sought treatment at our emergency department for an injury to their UE and also sought treatment at the orthopedics and traumatology clinic between the years 2013 and 2021 were manually scanned. The patients who applied to the Chest Diseases Clinic within 30 days after the trauma and were diagnosed with PE in the ICD code scan were included in the study. Results UE trauma was the cause of admission to the emergency department for 3,265 patients, and 21 of those patients (0.64%) were found to have PE. Fifteen of the patients were male, and six were female. The median age was 59 years (IQR 17). There were no deaths associated with PE. One of the patients had a scaphoid fracture, seven patients had a humerus fracture, five patients had a distal radius fracture, two patients had an acromioclavicular joint injury, one patient had a shoulder dislocation, one patient had a finger fracture, four patients had wrist crush injury. Three patients had diabetes mellitus. Five patients were active smokers. JAK-2 gene V617F mutation was detected in one patient. One patient was diagnosed with prostate cancer, and one had gastric cancer. One patient had a central venous catheter. Two patients were being treated for hypothyroidism. Two patients had hypertension. Conclusion According to the findings of our research, the probability of developing PE in the days following of an injury to the UE was found to be 0.64%. Patients with UE injuries who are active smokers and who also have diabetes, hypertension, hypothyroidism, cancer, coagulation disorder (JAK2 gene V617F mutation), or a central venous catheter may benefit from anticoagulant prophylaxis. This is because these patients are at a higher risk of developing dangerous blood clots.

PMID:37519534 | PMC:PMC10375827 | DOI:10.7759/cureus.41077

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PubMed articles on: Cancer & VTE/PE

Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis

Cureus. 2023 Jun 28;15(6):e41071. doi: 10.7759/cureus.41071. eCollection 2023 Jun.