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Clinical perspectives on the optimal use of lenalidomide plus bortezomib and dexamethasone for the treatment of newly diagnosed multiple myeloma.

To improve the outcomes of patients with the otherwise incurable hematologic malignancy of multiple myeloma (MM), a key paradigm includes initial treatment to establish disease control rapidly followed by maintenance therapy to ensure durability of response with manageable toxicity. However, patients' prognosis worsens after relapse, and the disease burden and drug toxicities are generally more challenging with subsequent lines of therapy. It is therefore particularly important that patients with newly diagnosed multiple myeloma (NDMM) receive optimal frontline therapy. The combination of lena

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… Notably, the incidence of cardiotoxicity was similar with high and standard doses of carfilzomib, although another systemic review and meta-analysis concluded that cardiovascular AE rates were higher with carfilzomib doses ≥45 mg/m2.83,84 In contrast, the bortezomib-associated risk of PN is known to … Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis. Leuk Lymphoma. 2018;59(11):2557-2569. 85. Shah JJ, Stadtmauer EA, Abonour R, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015;126(20):2284-2290. 86. …

Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats.

Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA),

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… CP administration has been linked to significant side effects, such as hemorrhagic cystitis, gonadotoxicity, nephrotoxicity, and cardiotoxicity, limiting its therapeutic use. Moreover, female patients who are treated with CP are susceptible to early menopause. … Efficacy of hesperidin on plasma, heart and liver tissue lipids in rats subjected to isoproterenol-induced cardiotoxicity Exp. Toxicol. Pathol. Off. J. Ges. Fur Toxikol. Pathol. 2012 64 449 452 10.1016/j.etp.2010.10.012 21095107 97. Al-Shahat A. Hulail M.A.E. Soliman N.M.M. Khamis T. Fericean L.M. …

Canine Gastric Cancer: Current Treatment Approaches.

Human gastric cancer (GC) ranks as the fifth most prevalent cancer worldwide, and is the third leading cause of cancer-related death. The incidence of GC is lower in dogs than in humans, accounting for less than 1% of all canine malignancies. In recent years, efforts have been made to understand the pathogenesis of GC and in find an appropriate therapy to maximize curative results, such as adjuvant chemotherapy treatments in addition to surgery. Although surgery is the first-line treatment, it is associated with several complications. In terms of chemotherapeutic intervention, canine gastric c

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… The dose-limiting toxicities associated with DOX therapy are infusion-rate-dependent hypersensitivity, myelosuppression, gastrointestinal toxicity, and a cumulative dose-related cardiotoxicity [ 10 , 29 , 30 , 31 ]. … Cardiotoxicity is rare in humans and has not been reported in dogs [ 29 , 30 , 31 ]. …

Pharmacovigilance in Cell and Gene Therapy: Evolving Challenges in Risk Management and Long-Term Follow-Up.

Cell and gene therapies, including CAR T-cells, CRISPR-based genome editing, and next-generation viral and non-viral delivery platforms, are transforming treatment paradigms across cancer, rare genetic disorders, immune dysregulation, and neurodegenerative disease. These therapies offer curative potential but also present safety challenges owing to prolonged biological activity, systemic immune engagement, and lasting genomic alterations. This review examines the range of related toxicities, including immune complications, genotoxicity, and organ-specific effects, with attention to atypical pr

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… AI and ML are being applied to large-scale RWD to detect rare or delayed complications, such as neurotoxicity or cardiotoxicity, earlier than traditional methods. …

From Pioneering Discoveries to Innovative Therapies: A Journey Through the History and Advancements of Nanoparticles in Breast Cancer Treatment.

Nanoparticle technology has revolutionized breast cancer treatment by offering innovative solutions addressing the gaps in traditional treatment methods. This paper aimed to comprehensively explore the historical journey and advancements of nanoparticles in breast cancer treatment, highlighting their transformative impact on modern medicine. The discussion traces the evolution of nanoparticle-based therapies from their early conceptualization to their current applications and future potential. We initially explored the historical context of breast cancer treatment, highlighting the limitations

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… The formulation in liposomes alters the pharmacokinetics and biodistribution of doxorubicin, which improves the efficacy and reduces cardiotoxicity relative to that of free doxorubicin. 121 , 122 These advantages make liposomal doxorubicin a promising NP-based therapy for breast cancer. … The liposomal encapsulation of doxorubicin in Doxil ® allowed for preferential drug accumulation in the tumor tissue by the EPR effect, reducing exposure in healthy tissues and mitigating the common cardiotoxicity of doxorubicin. 146 Figure 4 Nanoparticles’ impact on Immune response. …

Nature-Inspired Strategies in Cancer Management: The Potential of Plant Extracts in Modulating Tumour Biology.

Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer p

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… As a result, chemotherapy is associated with side effects such as hepatotoxicity, nephrotoxicity, ototoxicity, cardiotoxicity, neurotoxicity, and secondary cancers [ 10 , 11 , 12 ]. … Other side effects are related to the cardiotoxicity of chemotherapy drugs, which may lead to changes in blood pressure, electrocardiographic changes, arrhythmias, pericarditis, myocarditis, cardiomyopathy, heart attack, heart failure, or thrombosis [ 110 ]. …

Different types of amyloid concomitantly present in the same patients.

Different types of amyloid concomitantly present in the same patient is believed to be improbable. We reported four cases of patients with plasma cell disorders who were found to have biopsy proven concomitant different types of amyloid fibrils deposition. We characterized amyloid fibrils using immunogold electron microscopy. There is lack of experience in the treatment of these frail and elderly patients, who are on the threshold between necessity of chemotherapy for AL amyloidosis and necessity to avoid harmful treatment related toxicity. All patients with a systemic amyloid syndrome require

Keyword Index for Volume 95

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… 146, 1576 cancer-specific survival 1076 cannabinoid 197 cap-dependent translation 955 capecitabine 27, 1195 carboplatin 1309 carcinoembryonic antigen (CEA) 218, 674 carcinoembryonic antigen-related cell adhesion molecule 6 ( CEACAM6 ) 532 carcinoma of unknown primary 1309 carcinomas 1670 cardiotoxicity …

Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management.

BackgroundObesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity.MethodsA literature search using PubMed and Google Scholar was performed and the keywords 'obesity' and cancer' were used. The search was limited to research papers publish

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… Recent evidence also highlights that excess body fat has been associated with a high risk of treatment-related cardiotoxicity [ 115 , 116 ]. … Obesity As a Risk Factor for Anthracyclines and Trastuzumab Cardiotoxicity in Breast Cancer: A Systematic Review and Meta-Analysis. J. Clin. Oncol. 2016;34:3157–3165. doi: 10.1200/JCO.2016.67.4846. 116. …

Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.

Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in

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… AL amyloidosis has direct cardiotoxic, cytotoxic, and proapoptotic effects. 60 ATTR amyloidosis is due to the deposition of transthyretin protein. … The most concerning adverse effect is cardiotoxicity, which is due to the autophagy pathway and upregulation of protein phosphatase-2A activity and not due to proteasome inhibition. 78 Ixazomib is an oral and reversible PI. …

First-line therapy with daratumumab, lenalidomide and dexamethasone for patient with POEMS syndrome: A case report.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome) is a rare condition due to an underlying plasma cell neoplasm whose clinical presentation can be various so it could lead to delayed diagnosis and treatment. The pathogenesis of the syndrome is not well understood, and its therapy is adapted from other plasma cell disorders with the aim of alleviating symptoms, decreasing end-organ damage, improving quality of life and prolonging overall survival. We report a case of a 71 years-old woman who has been treated with continuous DRd (daratumumab, lenalid

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… About thalidomide, sensory neuropathy and cardiotoxicity are some of the prohibitive toxicities for its use in patients with POEMS syndrome [ 5 ]. Furthermore, according to specific peripheral neurotoxicity, bortezomib should be limited in patients without significant neurological symptoms [ 5 ]. …

Inflammation in Cardiomyopathies: Cellular Mechanisms Across Cardiac Phenotype.

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson-Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or v

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… In AL amyloidosis, soluble free light chains exert direct cardiotoxicity independent of fibril burden, initiating inflammatory and oxidative injury that accelerates ventricular dysfunction [ 32 ]. … Unlike aTTR, where fibril toxicity predominates, AL disease features an additional pathogenic component: soluble light chains are intrinsically cardiotoxic. …

Novel Strategies for Cancer Combat: Drug Combination Using Repurposed Drugs Induces Synergistic Growth Inhibition of MCF-7 Breast and HT-29 Colon Cancer Cells.

Our group developed a new model of drug combination consisting of the use of antineoplastic drugs and different repurposed drugs, having demonstrated that antimalarial and central nervous system (CNS) drugs have a promising anticancer profile as standalone agents, as well as in combined regimens. Here, we evaluated the anticancer profiles of two different CNS drugs (edaravone and quetiapine), both alone and in combination with antineoplastic agents for breast and colon cancer, to explore whether these repurposed drugs could synergistically enhance the anticancer potential of chemotherapeutic d

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… Nevertheless, the use of this drug is also limited by its cardiotoxicity and side effects. Moreover, the use of chemotherapeutics, particularly DOX, is associated with gonad toxicity, which leads to the induction of oxidative stress and consequently impairs ovarian function [ 5 ]. … Other studies also demonstrated that this drug, used in combination with antineoplastic agents, can reduce the side effects associated with chemotherapy, such as renal dysfunction [ 42 ], neurotoxicity [ 43 ], and cardiotoxicity [ 44 ]. …

Light Chain Stabilization: A Therapeutic Approach to Ameliorate AL Amyloidosis.

Non-native immunoglobulin light chain conformations, including aggregates, appear to cause light chain amyloidosis pathology. Despite significant progress in pharmacological eradication of the neoplastic plasma cells that secrete these light chains, in many patients impaired organ function remains. The impairment is apparently due to a subset of resistant plasma cells that continue to secrete misfolding-prone light chains. These light chains are susceptible to the proteolytic cleavage that may enable light chain aggregation. We propose that small molecules that preferentially bind to the nativ

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… Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity. Basic Res. Cardiol 2013, 108, 378. 16. Lavatelli F; Imperiini E; Orrù S; Rognoni P; Sarnataro D; Palladini G; Malpasso G; Soriano ME; Di Fonzo A; Valentini V; et al. … Zebrafish model of amyloid light chain cardiotoxicity: Regeneration versus degeneration. Am. J. Physiol. Circ. Physiol 2019, 316, H1158–H1166. 19. Shi J; Guan J; Jiang B; Brenner DA; del Monte F; Ward J; Connors L; Sawyer DB; Semigran MJ; Macgillivray TE; et al. …

Unveiling the unseen: navigating heart involvement in amyloidosis with biomarkers beyond the horizons of imaging.

Amyloidosis refers to a heterogenous group of systemic diseases characterized by the presence of a misfolded protein that deposits as amyloid fibrils in the interstitium of organs and tissues. The vast majority of cases of cardiac involvement (cardiac amyloidosis-CA) are due to immunoglobulin light chain (AL) amyloidosis, or transthyretin (ATTR) amyloidosis (either in its wild-type form-ATTRwt, or variant-ATTRv). The diagnostic workup of these diseases reflects the differences in terms of aetiology. Although imaging techniques represent fundamental tools in the diagnosis and follow-up of patie

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… leads to increased oxidative stress and apoptosis. 6 Oxidant stress results in direct impairment of cardiomyocyte contractility and relaxation with abnormal intracellular calcium handling. 6 The activation of p38 MAPK (mitogen-activated protein kinase) is one of the molecular mechanisms responsible for cardiotoxicity … by increasing oxidative stress and apoptosis. 7 This pathway also mediates B-type natriuretic peptide (BNP) transcription, supporting the association between cardiotoxic LC effects and elevated BNP levels. 7 Exposure of cardiac fibroblasts to cardiotropic immunoglobulin LCs translates into proteome …

Pazopanib in advanced soft tissue sarcomas.

Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma (STS). Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors, preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways. Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma, pazopanib was investigated in STS. A landm

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… over RECIST 1.1 in categorizing stable disease 47 , 48 Pharmacodynamic markers Hypertension | •No association of hypertension with improved PFS or OS in post-hoc analysis of aggregated phase II/III data 52 Other on-target toxic effects | •No association of drug-induced proteinuria, hypothyroidism or cardiotoxicity … A later analysis of other on-target toxicities within the same cohort found no association between the incidence of drug-induced proteinuria, hypothyroidism, or cardiotoxicity with survival 54 . …

Gaucher Disease Types I and III Responded Well to Substrate Reduction Therapy Using Eliglustat.

Gaucher disease (GD) causes the accumulation of glucocerebrosides in various organs, resulting in hepatosplenomegaly, anemia, decreased platelet counts, and bone disorders. Glucosylsphingosine accumulates in the brain and causes central nervous system (CNS) disorders. GD can be classified into types I (without CNS disorders), II, and III. Substrate reduction therapy (SRT) is an oral therapy that improves patients' quality of life; however, its effect on type III GD is unknown. We administered SRT to GD types I and III patients and found it effective. Malignancy is a late complication of GD, bu

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… Important adverse effects include arrhythmia and syncope owing to cardiotoxicity. As eliglustat is mainly metabolized by CYP2D6 , the CYP2D6 genotype should be confirmed before administration, since the genotype determines whether or not the drug can be administered and its dosage. …

Congestive heart failure associated with POEMS syndrome that was adequately distinguished from cardiac amyloidosis: a case report and literature review.

Congestive heart failure (CHF) is a common complication in patients with AL amyloidosis but is rare in another plasma cell dyscrasia, POEMS syndrome. A 52-year-old man developed POEMS syndrome with a solitary plasmacytoma complicated by CHF mimicking cardiac amyloidosis (CA). His neurological symptoms and CHF did not improve after radiotherapy (50 Gy) targeting the plasmacytoma. Based on typical findings of noninvasive examinations such as elevated serum NT-proBNP (12,631 pg/mL), a pseudo-infarct pattern on electrocardiography, interventricular septal thickening with a granular sparkling appea

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies.

Cancer represents the leading cause of disease-related death and treatment-associated morbidity in children with an increasing trend in recent decades worldwide. Nevertheless, the 5-year survival of childhood cancer patients has been raised impressively to more than 80% during the past decades, primarily attributed to improved diagnostic technologies and multiagent cytotoxic regimens. This strong benefit of more efficient tumor control and prolonged survival is compromised by an increased risk of adverse and fatal late sequelae. Long-term survivors of pediatric tumors are at the utmost risk fo

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… Besides SPMs, well-known late consequences of EBRT in pediatric cancer survivors comprise cardiotoxicity, endocrine effects, impact on growth, thyroid and gonadal dysfunction, genitourinary problems, and neurocognitive impairments [ 20 ]. … One of the most concerning side effects of CT is cardiotoxicity which can vary from subclinical myocardial dysfunction to irreversible and often fatal heart failure [ 45 ]. …

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research.

Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles t

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… The in vivo experiments in FR-overexpressing human cervical carcinoma KB tumor-bearing mice showed that both systems were active and able to reduce DOX-induced cardiotoxicity. … FA-liposome cardiotoxicity was comparable to that of Caelyx [ 131 ]. …