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DNA Damaging Drugs

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High prevalence of cardiovascular and respiratory abnormalities in advanced, intensively treated (transplanted) myeloma: The case for 'late effects' screening and preventive strategies.

OBJECTIVES: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors. METHODS: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off

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… However, both cardiotoxic chemotherapy and the late effects of other potentially cardiotoxic agents, such as multiple doses of ‘palliative’ thoracic radiotherapy, warrant consideration, both on a routine clinical basis, and in further clinical studies. … Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide. Bone Marrow Transplant. 2000;26:309–13. doi: 10.1038/sj.bmt.1702507. …

Cancer Immunotherapies: What the Perioperative Physician Needs to Know.

Purpose of reviewFor patients with cancer, treatment may include combination therapy, including surgery and immunotherapy. Here, we review perioperative considerations for the patient prescribed immunotherapeutic agents.Recent findingsThe perioperative period is a poignant moment in the journey of a patient with cancer, potentially deemed most influential compared to other moments in the care continuum. Several immunotherapeutic medications have been employed near the time of surgery to potentially increase effectiveness. Of the various drug classes, including immune checkpoint inhibitors, cyt

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… ICI-associated cardiotoxicity is relatively rare compared to other immune-related adverse effects. However, life-threatening ventricular tachyarrhythmias and complete atrioventricular block have been reported [ 15 ]. … Trastuzumab-induced cardiotoxicity: a review of clinical risk factors, pharmacologic prevention, and cardiotoxicity of other HER2-directed therapies. Breast Cancer Res Treat. 2021;188(1):21–36. doi: 10.1007/s10549-021-06280-x. 60. …

Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients.

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlappi

Supportive Care in Older Lymphoma Patients to Reduce Toxicity and Preserve Quality of Life

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… The definition of chemotherapy-related cardiotoxicity in the European Society of Cardiology (ESC) guidelines is a 10+% decrease in the left ventricular ejection fraction. … Mechanisms of Cardiotoxicity of Cancer Chemotherapeutic Agents: Cardiomyopathy and Beyond Can. J. Cardiol. 2016 32 863 870.e5 10.1016/j.cjca.2016.01.027 27117975 PMC4921299 95. Chung W.-B. Youn H.-J. Pathophysiology and Preventive Strategies of Anthracycline-Induced Cardiotoxicity Korean J. …

Atherosclerosis and the Bidirectional Relationship Between Cancer and Cardiovascular Disease: From Bench to Bedside, Part 2 Management.

The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a "syndemic" nature to these chronic diseases. We summarize management strategies targeting disor

Recent advances in understanding and treating immunoglobulin light chain amyloidosis.

Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body, resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical presentations and a tendency to mimic common medical conditions, AL amyloidosis is often diagnosed late and results in dismal outcomes. Early referral to a specialized center with expertise in management of AL amyloidosis is always recommended. The availability of sensitive biomarkers and novel therapies is reforming our approach to how we manage AL amy

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… Shi et al . proposed that the activation of p38 mitogen-activated protein kinase (MAPK) is one of the molecular mechanisms responsible for cardiotoxicity through an increase in cellular oxidative stress and apoptosis 11 . … It is important to note that p38 MAPK signaling is the same pathway that mediates type B natriuretic peptide (BNP) transcription, supporting an association between LC cardiotoxic effects with induced MAPK signaling and elevated BNP levels. …

Monoclonal Antibodies Approved for Cancer Therapy

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… Cutaneous : rash, nail disorders, pruritus Ado-trastuzumab emtansine x (Kadcyla ® ) | HER2 | Boxed warning : hepatotoxicity, cardiotoxicity, embryofetal toxicity. …

Nephrotoxicity of recent anti-cancer agents.

Cancer patients may develop a variety of kidney lesions that impair not only their immediate survival but also limit the adequate treatment of the underlying malignant process. This review summarizes the nephrotoxic potential of some of the most recently developed anti-cancer drugs, focusing on those interfering with the vascular endothelial growth factor and epidermal growth factor receptor pathways and mammalian target of rapamycin inhibitors. Thrombotic microangiopathy (haemolytic-uraemic syndrome), proteinuria, hypertension and magnesium depletion are the most common side effects. Also the

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… One of the clear examples of cancer therapy cardiotoxicity occurs in patients with breast cancer over-expressing the HER2 receptor, which is currently treated with anthracyclines or taxanes and with trastuzumab. Anthracyclines and trastuzumab are both associated with cardiotoxicity [ 86 ]. … Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102:14–25. doi: 10.1093/jnci/djp440. 87. Russo G, Cioffi G, Di LA, et al. …

Interventional Cardio-Oncology: Adding a New Dimension to the Cardio-Oncology Field.

The management of cardiovascular disease in patients with active cancer presents a unique challenge in interventional cardiology. Cancer patients often suffer from significant comorbidities such as thrombocytopenia and coagulopathic and/or hypercoagulable states, which complicates invasive evaluation and can specifically be associated with an increased risk for vascular access complications. Furthermore, anticancer therapies cause injury to the vascular endothelium as well as the myocardium. Meanwhile, improvements in diagnosis and treatment of various cancers have contributed to an increase i

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… Development of cardiotoxic side effects from chemotherapy depends on several factors including the choice of drug, dose of drug administered, interval of administration, cumulative dose, route of administration, and association with radiotherapy ( 10 ). … Cardiotoxicity with 5-fluorouracil and capecitabine: more than just vasospastic angina. Intern Med J (2010) 40(4)): :303–7. p. 10.1111/j.1445-5994.2009.02144.x 15. Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. …

Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting.

BACKGROUND: Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)-ubiquitin-proteasome-dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF-κB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study h

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… Enrico O, Gabriele B, Nadia C, Sara G, Daniele V, Giulia C, et al Unexpected cardiotoxicity in haematological bortezomib treated patients. Br J Haematol 2007;138:396–7. 66. … Nowis D, Maczewski M, Mackiewicz U, Kujawa M, Ratajska A, Wieckowski MR, et al Cardiotoxicity of the anticancer therapeutic agent bortezomib. Am J Pathol 2010;176:2658–68. 67. Xiao Y, Yin J, Wei J, Shang Z. …

Resveratrol and Other Natural Oligomeric Stilbenoid Compounds and Their Therapeutic Applications.

The use of natural compounds as an alternative to synthetic molecules has become a significant subject of interest in recent decades. Stilbenoids are a group of phenolic compounds found in many plant species and they have recently gained the focus of a multitude of studies in medicine and chemistry, resveratrol being the most representative molecule. In this review, we focused on the research that illustrates the therapeutic potential of this class of natural molecules considering various diseases with higher incidence rates. PubChem database was searched for bioactivities of natural stilbenoi

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… In this study, it was shown that the administration of isorhapontigenin 30 mg/kg/day, intraperitoneally, 3 weeks, significantly protected against doxorubicin-induced cardiotoxicity in mice. … Moreover, the inhibition of yes-associated protein 1 blocked the protective effects of isorhapontigenin on doxorubicin-induced cardiotoxicity [ 61 ]. …

Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results.

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have f

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… This increasing of ROS seems to play an important role in the cardiotoxicity caused by doxorubicin [ 197 ]. … For example, vitamin E could exert a cardioprotective effect but only against chronic cardiotoxicity, not against the development of chronic cardiomyopathy [ 198 ]. …

Emerging Therapies for Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and

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… Doxorubicin, a widely used chemotherapeutic agent, is known to cause off-target cardiotoxicity. … Doxorubicin delivered via N-acetylgalactosamine-conjugated PAMAM inhibited HepG2 xenograft in nude mice while providing protection from cardiotoxicity [ 31 ]. …

Chronic, self-reported fatigue in adult immunotherapy patients and healthy controls: No association with cardiopulmonary exercise testing parameters.

This study examined whether cardiopulmonary exercise test (CPET) performance parameters are associated with chronic cancer-related fatigue in patients receiving immunotherapy checkpoint inhibitors (ICI) and healthy controls. Also, the differences in energy expenditure of steady-state cycling and gross efficiency were assessed during submaximal cycling efforts. This study involved patients (n = 19, 48 ± 13 years) receiving PD-1, PD-L1 checkpoint inhibitors and controls of similar age (n = 21, 49 ± 17 years). During the first visit, data on medical history, previous physical activity records, an

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… However, since there were no specific diagnostic procedures applied to track cardiotoxicity development in this exploratory study, our suggestion remains theoretical and requires further research. … Longitudinal changes in skeletal muscle metabolism, oxygen uptake, and Myosteatosis during cardiotoxic treatment for early‐stage breast cancer. The Oncologist, 27, e748–e754. 10.1093/oncolo/oyac092 Lacey, J. , Lomax, A. …

Supporting treatment decision-making for patients with multiple myeloma post-DRd in Italy: a multi-criteria decision framework.

BACKGROUND: A substantial unmet medical need exists for patients with Multiple Myeloma ineligible for autologous stem cell transplantation who relapse after first-line therapy with daratumumab, lenalidomide and dexamethasone (DRd). Three therapeutic options recommended for lenalidomide-refractory patients from EHA-ESMO guidelines are approved in Europe and reimbursed in Italy: carfilzomib and dexamethasone (Kd); pomalidomide, bortezomib and dexamethasone (PVd); selinexor, bortezomib and dexamethasone (SVd). This study aimed to identify key decision criteria and their relevance for assessing th

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… Fourth, no adverse events related to cardiotoxicity, which is a known carfilzomib side-effect [ 45 , 46 ], were included among safety sub-criteria because no data on such events for SVd was available in the public domain. … Nevertheless, as highlighted by clinicians during the final workshop, since SVd is expected to have lower cardiotoxicity compared to both considered alternatives, its inclusion as a sub-criterion would have confirmed the obtained ranking. …

Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study.

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyr

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… McGowan JV Anthracycline chemotherapy and cardiotoxicity Cardiovasc. Drugs Ther. 2017 31 63 75 10.1007/s10557-016-6711-0 28185035 PMC5346598 20. Lenneman CG Sawyer DB Cardio-oncology: An update on cardiotoxicity of cancer-related treatment Circul. … Chien HC Kao Yang YH Bai JP Trastuzumab-related cardiotoxic effects in Taiwanese women: A nationwide cohort study JAMA Oncol. 2016 2 1317 1325 10.1001/jamaoncol.2016.1269 27310478 41. …

Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects.

(1) Background: Cancer is one of the leading causes of mortality worldwide. Radiotherapy and chemotherapy attempt to kill tumor cells by different mechanisms mediated by an intracellular increase of free radicals. However, free radicals can also increase in healthy cells and lead to oxidative stress, resulting in further damage to healthy tissues. Approaches to prevent or treat many of these side effects are limited. Ozone therapy can induce a controlled oxidative stress able to stimulate an adaptive antioxidant response in healthy tissue. This review describes the studies using ozone therapy

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… Oxidative stress remains the most probable mechanism for the DOX-induced cardiotoxic effect, mediated by the production of iron-complex and the subsequent generation of free radicals [ 15 , 16 ]. … In selected patients, Dexrazoxane can be used to prevent/diminish DOX-induced cardiotoxicity, because Dexrazoxane is an iron chelator that decreases the DOX-iron binding and the subsequent free radical generation. 2.4. …

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

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… Biomarkers (i.e., troponins, natriuretic peptides, nitric oxid metabolites, and microRNAs) also appear to be important for the detetection of patients at increased risk of CAR-T cardiotoxicity, both in adult and pediatric patients [ 46 , 47 ]. … CAR T Cell Therapy-Related Cardiovascular Outcomes and Management: Systemic Disease or Direct Cardiotoxicity? JACC CardioOncol. 2020;2:97–109. doi: 10.1016/j.jaccao.2020.02.011. 44. …

Molecular Delivery of Cytotoxic Agents via Integrin Activation.

Integrins are cell adhesion receptors overexpressed in tumor cells. A direct inhibition of integrins was investigated, but the best inhibitors performed poorly in clinical trials. A gained attention towards these receptors arouse because they could be target for a selective transport of cytotoxic agents. Several active-targeting systems have been developed to use integrins as a selective cell entrance for some antitumor agents. The aim of this review paper is to report on the most recent results on covalent conjugates between integrin ligands and antitumor drugs. Cytotoxic drugs thus conjugate

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… Cytotoxic Antibiotics Doxorubicin and Daunorubicin Doxorubicin (DOX) is a broadly used and effective anticancer agent but it is cause of cardiotoxicity [ 59 ]. … DOX is one of the most effective chemotherapy drugs, but the low tumor selectivity and side effects such as cardiotoxicity greatly affected the curative effect [ 60 ]. …