Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death

Anthracycline antineoplastic agents such as doxorubicin are widely used and highly effective component of adjuvant chemotherapy for breast cancer and curative regimens for lymphomas, leukemias, and sarcomas. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that typically manifests as cardiomyopathy and can progress to the potentially fatal clinical syndrome of heart failure. Decades of pre-clinical research have explicated the complex and multifaceted mechanisms of anthracycline-induced cardiotoxicity. It is well-established that oxidative stress contributes to the pathobiology and recent work has elucidated important central roles for direct mitochondrial injury and iron overload. Here we focus instead on emerging aspects of anthracycline-induced cardiotoxicity that may have received less attention in other recent reviews: thrombosis, myocardial atrophy, and non-apoptotic programmed cell death.

The Essential Properties of Nanoemulsions

Nanoemulsions are a submicron with colloidal particulate systems ranging from 10 to 1,000 nm in size. Nanoemulsions hold enormous scope in the field of cosmetics, diagnostics, food, and paint. Moreover, nanoemulsions are ubiquitously regarded as superior drug carriers for the infusion of lipophilic cytotoxic antineoplastic agents on a particular target criterion. Nanoemulsions are prepared from two immiscible liquids that are mixed by employing surfactants and co-surfactants. It also encompasses some significant benefits like biocompatibility, non-immunogenicity, low toxicity, drug entrapment, nanoscale size, large surface area, long-term and restrained release, uncomplicated mode of formulation, as well as thermodynamic stability. Nanoemulsion drug delivery can address the major challenge of effective drug formulation due to its instability and poor solubility in the vehicle. The primary objective of this chapter is to provide a quick overview of various physico-properties of nanoemulsion, with a special emphasis on its various applications in various fields.

Antineoplastic agents used in pediatric hematopoietic bone marrow transplantation: a review about pharmacology and pharmaceutical issues.

This article proposes the characterization of the main chemotherapeutic agents used in hematopoietic stem cell transplantation in pediatric patients, carrying out a review of the main pharmacological and pharmacokinetic characteristics that are peculiar to children, as well as technical aspects for the handling, prescription, and administration of each one of these. It is extremely important that all professionals know how to recognize the characteristics of each drug and how its peculiarities impact the quality of patient's treatment, being able to predict and propose necessary interventions for potential problems of therapy, which can be identified and measured.

Local control of bone metastases treated with external beam radiotherapy in recent years: a multicenter retrospective study

Background Over the past decades, remarkable advancements in systemic drug therapy have improved the prognosis of patients with bone metastases. Individualization is required in external beam radiotherapy (EBRT) for bone metastases according to the patient’s prognosis. To establish individualized EBRT for bone metastases, we investigated factors that affect the local control (LC) of bone metastases. Methods Between January 2010 and December 2019, 536 patients received EBRT for 751 predominantly osteolytic bone metastases. LC at EBRT sites was evaluated with a follow-up computed tomography. The median EBRT dose was biologically effective dose (BED10) (39.0) (range of BED10: 14.4–71.7 Gy). Results The median follow-up time and median time of computed tomography follow-up were 11 (range 1–123) months and 6 (range 1–119) months, respectively. The 0.5- and 1-year overall survival rates were 73% and 54%, respectively. The 0.5- and 1-year LC rates were 83% and 79%, respectively. In multivariate analysis, higher age (≥ 70 years), non-vertebral bone metastases, unfavorable primary tumor sites (esophageal cancer, colorectal cancer, hepatobiliary/pancreatic cancer, renal/ureter cancer, sarcoma, melanoma, and mesothelioma), lower EBRT dose (BED10 < 39.0 Gy), and non-administration of bone-modifying agents (BMAs)/antineoplastic agents after EBRT were significantly unfavorable factors for LC of bone metastases. There was no statistically significant difference in the LC between BED10 = 39.0 and BED10 > 39.0 Gy. Conclusions Regarding tumor-related factors, primary tumor sites and the sites of bone metastases were significant for the LC. As for treatment-related factors, lower EBRT doses (BED10 < 39.0 Gy) and non-administration of BMAs/antineoplastic agents after EBRT were associated with poor LC. Dose escalation from BED10 = 39.0 Gy did not necessarily improve LC.

How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: a Perspective on the Role of PPT1 Enzyme

: Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon, etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here, we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin (mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of antimalarial and antineoplastic agents in cancer cells.

Antineoplastics Encapsulated in Nanostructured Lipid Carriers

Ideally, antineoplastic treatment aims to selectively eradicate cancer cells without causing systemic toxicity. A great number of antineoplastic agents (AAs) are available nowadays, with well-defined therapeutic protocols. The poor bioavailability, non-selective action, high systemic toxicity, and lack of effectiveness of most AAs have stimulated the search for novel chemotherapy protocols, including technological approaches that provide drug delivery systems (DDS) for gold standard medicines. Nanostructured lipid carriers (NLC) are DDS that contain a core of solid and lipid liquids stabilised by surfactants. NLC have high upload capacity for lipophilic drugs, such as the majority of AAs. These nanoparticles can be prepared with a diversity of biocompatible (synthetic or natural) lipid blends, administered by different routes and functionalised for targeting purposes. This review focused on the research carried out from 2000 to now, regarding NLC formulations for AAs (antimetabolites, antimitotics, alkylating agents, and antibiotics) encapsulation, with special emphasis on studies carried out in vivo. NLC systems for codelivery of AAs were also considered, as well as those for non-classical drugs and therapies (natural products and photosensitisers). NLC have emerged as powerful DDS to improve the bioavailability, targeting and efficacy of antineoplastics, while decreasing their toxic effect in the treatment of different types of cancer.

The Infusion Center

Availability of more effective supportive therapies coupled with emergence of novel antineoplastic agents has facilitated administration of cancer treatments outside the hospital setting. Cancer treatments typically require multiple visits. Accordingly, it can be exhausting for patients and their caregivers who are already under a lot of stress including physical, emotional and financial strain, among others. Infusion centers allow providers to help patients better manage and control their disease and associated symptoms by providing a continuity of care throughout their medical need, enhancing continuity of care and improving compliance. Here, we described the major components required for successful operation of a cancer infusion center. The ultimate goal is to offer a patient-centered experience that improves the overall quality of delivered care at a sustainable cost.

Identification of antineoplastic agents for oral squamous cell carcinoma: an integrated bioinformatics approach using differential gene expression and network biology

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial neoplasm and anatomical subtype of head and neck squamous cell carcinoma (HNSCC) with an average 5-year survival rate of less than 50%. To improve the survival rate of OSCC, the discovery of novel anti-cancer drugs is urgently needed. In the present study, we performed metanalysis of 5 gene expression datasets (GSE23558, GSE25099, GSE30784, GSE37991 and TCGA-OSCC) that resulted in 1851 statistically significant DEGs in OSCC. The DEGs were involved in key biological pathways that drive the progression of OSCC. A comprehensive protein-protein interaction (PPI) network was constructed from the DEGs and the top protein clusters (modules) were extracted in Cytoscape. The DEGs from the top modules were searched for antineoplastic agents using L1000CDS2 server. The search resulted in a total of 37 perturbing agents from which 12 well-characterized antineoplastic agents were selected. The selected 12 antineoplastic agents namely Teniposide, Palbociclib, Etoposide, Fedratinib, Tivozanib, Afatinib, Vemurafenib, Mitoxantrone, Idamycin, Canertinib, Dovitinib and Selumetinib. These drugs showed interactions with the over expressed hub genes that regulate cellular proliferation and growth in OSCC progression. These identified antineoplastic agents are candidates for their potential role in treating OSCC.