ABSTRACT
The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J Mir34a-/-mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.
PMID:32585876 | DOI:10.3390/ijms21124454
07:23
PubMed articles on: Cardio-Oncology
SGLT2i: beyond the glucose-lowering effect
Ni L, et al. Cardiovasc Diabetol 2020 - Review.
ABSTRACT
Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.
PMID:32590982 | PMC:PMC7320582 | DOI:10.1186/s12933-020-01071-y
07:23
PubMed articles on: Cardio-Oncology
Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects
Ashrafizadeh M, et al. Life Sci 2020 - Review.
ABSTRACT
Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.
PMID:32593707 | DOI:10.1016/j.lfs.2020.117984
07:23
PubMed articles on: Cancer & VTE/PE
Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE
Weitz JI, et al. J Thromb Thrombolysis 2020.
ABSTRACT
Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE (ClinicalTrials.gov: NCT02155491) is a prospective, observational study of 10,684 patients with objectively diagnosed VTE from 415 sites in 28 countries. We compared baseline characteristics, VTE treatment patterns, and 1-year outcomes (mortality, recurrent VTE and major bleeding) in 1075 patients with active cancer, 674 patients with a history of cancer, and 8935 patients without cancer. Patients with active cancer and history of cancer were older than cancer-free patients, with median ages of 64.8, 68.9, and 58.4 years, respectively. The most common sites of active cancer were lung (14.5%), colorectal (11.0%), breast (10.6%), and gynaecological (10.3%). Active cancer patients had a higher incidence of upper limb and vena cava thrombosis than cancer-free patients (9.0% vs 4.8% and 5.1% vs 1.4%, respectively), and were more likely to receive parenteral anticoagulation as monotherapy than cancer-free patients (57.8% vs 12.1%), and less likely to receive DOACs (14.2% vs 50.6%). Rates of death, recurrent VTE, and major bleeding were higher in active cancer patients than in cancer-free patients, with hazard ratios (95% confidence intervals) of 14.2 (12.1-16.6), 1.6 (1.2-2.0) and 3.8 (2.9-5.0), respectively. VTE was the second most common cause of death in patients with active cancer or history of cancer. In patients with VTE, those with active cancer are at higher risk of death, recurrence, and major bleeding than those without cancer.
PMID:32583306 | DOI:10.1007/s11239-020-02180-x
07:23
PubMed articles on: Cardio-Oncology
A Series of Novel HDAC Inhibitors with Anthraquinone as a Cap Group
Zou Y, et al. Chem Pharm Bull (Tokyo) 2020.
ABSTRACT
Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displayed the comparable inhibition in enzymatic activity and cell proliferation than that of Vorinostat (SAHA). Notably, compound 4b showed certain selectivity of antiproliferative effects on cancer cell lines over non-cancer cell lines.
PMID:32611998 | DOI:10.1248/cpb.c20-00206
07:23
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PubMed articles on: Cardio-Oncology
Breast Cancer Survivorship, Quality of Life, and Late Toxicities
Nardin S, et al. Front Oncol 2020 - Review.
ABSTRACT
Breast cancer is the most frequent cancer in women: in 2018, almost two million cases have been diagnosed all over the world and it represents the principal cause of death from a neoplastic disease in women. In the past years, breast cancer prognosis has significantly improved over time: currently 5-year survival rates are in the range of 90%, and 10-year survival is about 80%. This improvement has been mostly observed in western countries, due to high coverage and compliance with screening programs, leading to early diagnosis, i.e., when the disease is at a subclinical level, and to an improvement in tumor molecular characterization and innovative systemic treatments. Yet the identification of different biological breast cancer subtypes prompted the development of innovative targeted agents and improved treatment personalization. On the other hand, longer survival rates and increasing proportions of cured patients require dedicated strategies to manage long-term sequelae of breast cancer treatments, with particular attention to quality of life. This review analyzes the most important issues, potentially occurring with cancer treatments, concerning long-term sequelae and quality of life, to define a global approach to breast cancer survivorship.
PMID:32612947 | PMC:PMC7308500 | DOI:10.3389/fonc.2020.00864
07:23
PubMed articles on: Cardio-Oncology
Trastuzumab-induced cardiotoxicity and role of mitochondrial connexin43 in the adaptive response
Pecoraro M, et al. Toxicol In Vitro 2020 - Review.
ABSTRACT
Trastuzumab, the humanized monoclonal antibody specific for HER2 receptor, is the gold standard in the treatment of HER2+ breast cancer. Despite its high therapeutic efficacy, cardiotoxicity has emerged as a significant side effect. The molecular mechanisms involved are not well understood, but all converge on mitochondria. Mitochondrial Cx43 can confer cardioprotection by regulating mitochondrial calcium homeostasis, ROS production and propagation of apoptotic signals, and studies report that it is overexpressed both in ischemic preconditioning and in Doxorubicin-induced cardiotoxicity. This study was designed to evaluate whether mitochondrial Cx43 (mCx43) is also involved in Trastuzumab-induced cardiotoxicity. Here we demonstrated that mCx43 is overexpressed in Trastuzumab-treated H9c2 cells. Our data showed that inhibition of Cx43 translocation to mitochondria, obtained by radicicol pre-treatment, significantly increases cytosolic and mitochondrial superoxide formation, mitochondrial membrane depolarization and the consequent apoptosis induced by Trastuzumab. Our results support the hypothesis that disruption of mitochondrial function is the principal mechanism by which Trastuzumab elicits its cardiotoxicity and mCx43 appears to counteract the Trastuzumab-induced mitochondrial damage.
PMID:32599261 | DOI:10.1016/j.tiv.2020.104926
07:23
PubMed articles on: Cancer & VTE/PE
Deep Venous Thrombosis in a Patient with a Moderate Pretest Probability and a Negative D-Dimer Test: A Review of the Diagnostic Algorithms
Al-Khafaji RA and Schierbeck L. J Blood Med 2020 - Review.
ABSTRACT
Modern diagnostic strategies of venous thromboembolism (VTE) have been developed. In this review, the diagnostic algorithms for deep-vein thrombosis (DVT) and their parameters are discussed individually in the context of reporting a case of DVT in a 43-year-old Caucasian female with a moderate pretest probability stratified by Wells' score and a negative high quality D-dimer test. The patient was on treatment with Xarelto (rivaroxaban), 20 mg PO daily at the time of presentation. The diagnosis was verified through a complete lower limb ultrasound (US). This case highlights the diagnostic challenges and pitfalls of the current algorithms, especially those seen in a subgroup of patients such as patients with cancer, pregnancy, recurrent VTE or are on anticoagulation therapy at the time of presentation. The diagnosis of DVT is less plausible in a patient who is on anticoagulation therapy, but physicians should be aware of such a possibility. Physicians should also know in advance the numerous clinically relevant limitations of D-dimer testing before interpreting the results. Unifying the current diagnostic strategies, modifying the current Wells' score and using the protocol of a whole-leg compression US instead of the limited US protocol are among the several cautious suggestions that have been proposed based on this review to possibly decrease the incidence of missed DVT.
PMID:32581617 | PMC:PMC7266946 | DOI:10.2147/JBM.S244773
07:23
PubMed articles on: Cancer & VTE/PE
Surgical Venous Thromboembolism Prophylaxis: Clinical Practice Update
Segon YS, et al. Hosp Pract (1995) 2020.
ABSTRACT
<underlineBackground: Perioperative medicine continues to evolve as new literature emerges. This article provides an update on prevention of venous thromboembolism (VTE) in surgical patients.
METHODS: We reviewed articles on VTE prevention in surgical patients published in peer reviewed journals since the publication of 2012 ACCP guidelines on VTE prevention in surgical patients.
RESULTS: Methods of VTE prophylaxis include aggressive ambulation, mechanical prophylaxis and pharmacological prophylaxis. In non-orthopedic surgery, the overall approach remains assessment of thrombosis risk with the recommendation to use a risk assessment tool such as the modified Caprini score. Low molecular weight heparin (LMWH) appears to be more effective than unfractionated heparin (UFH) for VTE prophylaxis in non-orthopedic surgery. For orthopedic surgery, recent studies now recognize aspirin as an option for VTE prophylaxis after total hip arthroplasty, total knee arthroplasty and hip fracture surgery. Extended prophylaxis with LMWH reduces the risk of symptomatic VTE in high risk abdominal and pelvic cancer surgery without an appreciable increase in risk of bleeding and decreased symptomatic VTE in major orthopedic surgery but with more minor but not major bleeding. Prophylactic Inferior vena cava (IVC) filter placement or surveillance compression ultrasonography is not recommended in management or detection of VTE in surgical patients.
CONCLUSIONS: This article aims to provide insight into data from last several years which has potential to change clinical practices in perioperative setting.
PMID:32589468 | DOI:10.1080/21548331.2020.1788893
07:23
PubMed articles on: Cardio-Oncology
Incidence and Onset of Severe Cardiac Events After Radiotherapy for Esophageal Cancer
Wang X, et al. J Thorac Oncol 2020.
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