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Critical Reviews in Analytical Chemistry 2023Epirubicin (EPI) is a chemotherapeutic agent belonging to the anthracycline drug class indicated for treating several tumors. It acts by suppressing the DNA and RNA... (Review)
Review
Epirubicin (EPI) is a chemotherapeutic agent belonging to the anthracycline drug class indicated for treating several tumors. It acts by suppressing the DNA and RNA synthesis by intercalating between their base pair. However, several side effects are associated with this therapy, including cardiotoxicity and myelosuppression. Therefore, EPI delivery in nanosystems has been an interesting strategy to overcome these limitations and improve the safety and efficacy of EPI. Thus, analytical methods have been used to understand and characterize these nanosystems, including spectrophotometric, spectrofluorimetric, and chromatography. Spectrophotometric and spectrofluorimetric methods have been used to quantify EPI in less complex matrices due to their efficiency, low cost, and green chemistry character. By contrast, high-performance liquid chromatography is a suitable method for detecting EPI in more complex matrices (e.g., plasm and urine) owing to its high sensitivity. This review summarizes physicochemical and pharmacokinetic properties of EPI, its application in drug delivery nanosystems, and the analytical methods employed in its quantification in different matrices, including blood, plasm, urine, and drug delivery nanosystems.
Topics: Epirubicin; Nanoparticles; Drug Delivery Systems; Antibiotics, Antineoplastic
PubMed: 34818953
DOI: 10.1080/10408347.2021.2007469 -
Cancer Chemotherapy and Pharmacology Jul 2019Chemobrain refers to a common sequela experienced by a substantial subset of cancer patients exposed to chemotherapeutic treatment, a phenomenon that dramatically... (Review)
Review
Chemobrain refers to a common sequela experienced by a substantial subset of cancer patients exposed to chemotherapeutic treatment, a phenomenon that dramatically deteriorates the survivors' quality of life and prevents them from restoring their pre-cancer life. This review is intended to address the current knowledge regarding the mechanisms underlying the pathophysiology of the chemobrain phenomenon, with special focus on the antineoplastic agent ''doxorubicin'', which has been shown to be implicated in strenuous central neurotoxicity despite being-almost entirely-peripherally confined. Moreover, the assessment of the post-chemotherapy cognitive impairment in both human and animal subjects, and the potential pharmacotherapy and behavioral intervention strategies are reviewed.
Topics: Animals; Antibiotics, Antineoplastic; Brain; Cognition; Cognition Disorders; Doxorubicin; Humans; Neoplasms; Quality of Life
PubMed: 30955080
DOI: 10.1007/s00280-019-03827-0 -
Molecular Cancer Therapeutics Jun 2021Calicheamicin antibody-drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin)...
Calicheamicin antibody-drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin) targeting CD33 for acute myeloid leukemia and Besponsa (inotuzumab ozogamicin) targeting CD22 for acute lymphocytic leukemia. Both of these calicheamicin ADCs are heterogeneous, aggregation-prone, and have a shortened half-life due to the instability of the acid-sensitive hydrazone linker in circulation. We hypothesized that we could improve upon the heterogeneity, aggregation, and circulation stability of calicheamicin ADCs by directly attaching the thiol of a reduced calicheamicin to an engineered cysteine on the antibody via a disulfide bond to generate a linkerless and traceless conjugate. We report herein that the resulting homogeneous conjugates possess minimal aggregation and display high stability with 50% of the drug remaining conjugated to the antibody after 21 days. Furthermore, these calicheamicin ADCs are highly efficacious in mouse models of both solid tumor (HER2 breast cancer) and hematologic malignancies (CD22 non-Hodgkin lymphoma). Safety studies in rats with this novel calicheamicin ADC revealed an increased tolerability compared with that reported for Mylotarg. Overall, we demonstrate that applying novel linker chemistry with site-specific conjugation affords an improved, next-generation calicheamicin ADC.
Topics: Animals; Antibiotics, Antineoplastic; Calicheamicins; Disease Models, Animal; Humans; Immunoconjugates; Mice
PubMed: 33722856
DOI: 10.1158/1535-7163.MCT-20-0035 -
Cancer therapeutics-related cardiovascular dysfunction: Basic mechanisms and clinical manifestation.Journal of Cardiology Mar 2023Although recent advances in cancer treatment improve cancer prognosis, cancer therapeutics-related cardiovascular dysfunction (CTRCD) significantly contributes to the... (Review)
Review
Although recent advances in cancer treatment improve cancer prognosis, cancer therapeutics-related cardiovascular dysfunction (CTRCD) significantly contributes to the global burden of cardiovascular disease. CTRCD causes two crucial issues: first, premature treatment interruption or discontinuation of chemotherapy; second, the development of congestive heart failure during and after cancer treatment. Thus, early detection and prompt treatment of CTRCD may improve the prognosis in cancer patients. This review covers representative anticancer drugs, including anthracyclines, human epidermal growth factor 2 inhibitors, tyrosine kinase inhibitors, proteasome inhibitors, and immune checkpoint inhibitors. We focus on the molecular mechanisms of CTRCD and various approaches to diagnosis, prevention, monitoring, and treatment.
Topics: Humans; Cardiotoxicity; Early Detection of Cancer; Antineoplastic Agents; Antibiotics, Antineoplastic; Neoplasms
PubMed: 35589463
DOI: 10.1016/j.jjcc.2022.04.006 -
Journal of Oncology Pharmacy Practice :... Mar 2020Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the... (Review)
Review
BACKGROUND
Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the two main obstacles to doxorubicin therapy are drug-induced cardiotoxicity and drug resistance.
METHOD
The study utilizes systemic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar, and Cochrane. The study utilizes secondary information obtained from health organizations using filters and keywords to sustain information relevancy. The study utilizes information retrieved from studies captured in the peer-reviewed journals on "doxorubicin-induced cardiotoxicity" and "doxorubicin resistance."
DISCUSSION AND RESULTS
The exact mechanisms of cardiotoxicity are not known; various hypotheses are studied. Doxorubicin can lead to free radical generation in various ways. The commonly proposed underlying mechanisms promoting doxorubicin resistance are the expression of multidrug resistance proteins as well as other causes.
CONCLUSION
In this review, we have described the major obstacles to doxorubicin therapy, doxorubicin-induced cardiotoxicity as well as the mechanisms of cancer drug resistance and in following the treatment failures.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Cardiotoxins; Cardiovascular Diseases; Doxorubicin; Drug Resistance, Neoplasm; Endothelium, Vascular; Humans; Neoplasms
PubMed: 31594518
DOI: 10.1177/1078155219877931 -
Experimental Neurology Feb 2020Chemotherapy has significantly increased the number of cancer survivors. However, chemotherapy itself carries various adverse effects that limit the efficacy of... (Review)
Review
Chemotherapy has significantly increased the number of cancer survivors. However, chemotherapy itself carries various adverse effects that limit the efficacy of treatment and quality of life of the cancer patients. Most patients who have received chemotherapy report some cognitive deficit characterized by dysfunction in memory, learning, concentration, and reasoning. The phenomenon of cognitive decline developed from chemotherapy treatment is referred to as chemotherapy-induced cognitive impairment (CICI) or chemobrain. The two most common cancers occurring worldwide are lung and breast cancer. The predominant chemotherapeutic drugs used to treat lung and breast cancer are doxorubicin and cisplatin. There is evidence to suggest that both drugs potentially induce chemobrain. The evidence around the proposed pathogenesis of chemobrain caused by these two drugs is inconsistent. Understanding the underlying mechanisms involved in the development of chemobrain would aid in the prevention or treatment of the adverse effects of chemotherapy on brain. This review will summarize and discuss controversial findings and possible mechanisms involved in the development of chemobrain and the interventions which could limit it from in vitro, in vivo, and clinical studies.
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cisplatin; Cognition Disorders; Cognitive Dysfunction; Doxorubicin; Humans; Neoplasms
PubMed: 31756316
DOI: 10.1016/j.expneurol.2019.113118 -
Journal of Ethnopharmacology Jul 2019Plant-specific fungus of natural compound of Ascochyta viciae has traditionally been used in the treatment of sleeping sickness and tumors. The anti-tumor activities of...
ETHNOPHARMACOLOGICAL RELEVANCE
Plant-specific fungus of natural compound of Ascochyta viciae has traditionally been used in the treatment of sleeping sickness and tumors. The anti-tumor activities of the compounds obtained from Pisum sativum L were evaluated in this study.
AIM OF THE STUDY
In this study, during the prolonged incubation, treatment of the LPS-stimulated tumor-like macrophage RAW 264.7 cells with ASC exhibited the shift of anti-inflammatory behavior to a type of necroptotic cell death named necroptosis.
MATERIALS AND METHODS
Ascochlorin (ASC) purified from plant-specific fungus Ascochyta viciae is a natural compound with the trimethyl oxocyclohexyl structure and an anti-cancer and antibiotic agent. The fungus contributes to the Ascochyta blight disease complex of pea (Pisum sativum L). RAW 264.7 cells have been stimulated with LPS and treated with ASC. Cell viability of the LPS-treated RAW 264.7 cells and bone marrow-derived macrophage (BMDM) cells were examined. Flow cytometry analysis with 7AAD and Annexin V was examined for the apoptotic or necroptosis/late-apoptosis. Cleaved caspase-3, -7 and -8 as well as cleaved PARP were assessed with a caspase inhibitor, z-VAD-fmk. LPS-responsible human leukemic U937 and colon cancer SW480 and HT-29 cells were also examined for the cell viabilities.
RESULTS
Flow cytometry analysis after Annexin V and 7AAD double staining showed that ASC alone induces apoptosis in RAW 264.7 cells, while it induces necroptosis/late-apoptosis in LPS-treated RAW 264.7 cells. 7AAD and Annexin V positive populations were increased in the LPS-treated cells with ASC. Although viability of LPS-treated cells with ASC was decreased, the amounts of cleaved caspase-3, -7 and -8 as well as cleaved PARP were reduced when compared with ASC-treated cells. Upon ASC treatment, the cleaved caspase-8 level was not changed, however, cleaved caspase-3, -7, and PARP were reduced in LPS-stimulated RAW 264.7 cells treated with ASC, claiming a caspase-8 independent necroptosis of ASC. Furthermore, ASC and LPS-cotreated cells which a caspase inhibitor, z-VAD-fmk, was pretreated, showed the decreased cell viability compared with control cells without the inhibitor. Cell viability of RAW 264.7 cells co-treated with ASC and LPS when treated with z-VAD was decreased. In the LPS-responsible human leukemic U937 and colon cancer SW480 and HT-29 cells, cell viabilities were decreased by 10 μM ASC.
CONCLUSION
Prolonged stimulation of ASC with LPS induces the necroptosis in RAW cells. Activated immune cells may share the susceptibility of antitumor agents with the cancer cells.
Topics: Alkenes; Animals; Antibiotics, Antineoplastic; Apoptosis; Caspases; Cell Line, Tumor; Humans; Lipopolysaccharides; Mice; Necrosis; Phenols; RAW 264.7 Cells
PubMed: 31028855
DOI: 10.1016/j.jep.2019.111898 -
Seminars in Cell & Developmental Biology Feb 2020Anthracyclines Doxorubicin, Epirubicin, Daunorubicin and Idarubicin are used to treat a variety of tumor types in the clinics, either alone or, most often, in... (Review)
Review
Anthracyclines Doxorubicin, Epirubicin, Daunorubicin and Idarubicin are used to treat a variety of tumor types in the clinics, either alone or, most often, in combination therapies. While their cardiotoxicity is well known, the emergence of chemoresistance is also a major issue accounting for treatment discontinuation. Resistance to anthracyclines is associated to the acquisition of multidrug resistance conferred by overexpression of permeability glycoprotein-1 or other efflux pumps, by altered DNA repair, changes in topoisomerase II activity, cancer stemness and metabolic adaptations. This review further details the metabolic aspects of resistance to anthracyclines, emphasizing the contributions of glycolysis, the pentose phosphate pathway and nucleotide biosynthesis, glutathione, lipid metabolism and autophagy to the chemoresistant phenotype.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Drug Resistance, Neoplasm; Humans; Molecular Structure; Neoplasms
PubMed: 31112797
DOI: 10.1016/j.semcdb.2019.05.006 -
Life Sciences Apr 2020Conventional cancer therapies such as chemotherapy, radiation therapy, and immunotherapy due to the complexity of cancer have been unsuccessful in the complete... (Review)
Review
Conventional cancer therapies such as chemotherapy, radiation therapy, and immunotherapy due to the complexity of cancer have been unsuccessful in the complete eradication of tumor cells. Thus, there is a need for new therapeutic strategies toward cancer. Recently, the therapeutic role of bacteria in different fields of medicine and pharmaceutical research has attracted attention in recent decades. Although several bacteria are notorious as cancer-causing agents, recent research revealed intriguing results suggesting the bacterial potential in cancer therapy. Thus, bacterial cancer therapy is an alternative anticancer approach that has promising results on tumor cells in-vivo. Moreover, with the aid of genetic engineering, some natural or genetically modified bacterial strains can directly target hypoxic regions of tumors and secrete therapeutic molecules leading to cancer cell death. Additionally, stimulation of immune cells by bacteria, bacterial cancer DNA vaccine and antitumor bacterial metabolites are other therapeutic applications of bacteria in cancer therapy. The present study is a comprehensive review of different aspects of bacterial cancer therapy alone and in combination with conventional methods, for improving cancer therapy.
Topics: Animals; Antibiotics, Antineoplastic; Bacteria; Combined Modality Therapy; Genetic Engineering; Humans; Immunotherapy; Neoplasms
PubMed: 32032647
DOI: 10.1016/j.lfs.2020.117398 -
Applied Microbiology and Biotechnology Sep 2020The aureolic acid-type polyketide mithramycin (MTM) has a remarkable cytotoxicity against a variety of human tumors and has been used for the treatment of several types... (Review)
Review
The aureolic acid-type polyketide mithramycin (MTM) has a remarkable cytotoxicity against a variety of human tumors and has been used for the treatment of several types of cancer, including chronic and acute myeloid leukemia, testicular carcinoma, hypercalcemia, and Paget's disease. However, its clinical use is quite limited due to its toxicity. Recently, interest in MTM has been renewed after its identification as a top candidate for the inhibition of the aberrant fusion transcription factor EWS-FLI1, associated with malignant transformation and progression of Ewing sarcoma tumor family. The mechanism of MTM inhibition involves its reversible non-intercalative interaction with GC-rich DNA regions. As a result of this binding, MTM blocks binding of transcription factors (such as Sp1) to their GC-rich promoters and inhibits transcription of several proto-oncogenes and thus suppresses various types of cancer. Knowledge of the biosynthesis of MTM and its gene cluster has enabled genetic modifications of the gene cluster and combinatorial biosynthesis to produce new modified MTM molecules ("mithralogues") with improved efficacy and lower toxicity, which has also renewed interest in the clinical development of MTM. However, production yields of MTM and its analogues are low in the natural production strains. Recent developments in genetic engineering approaches have made it possible to increase MTM production through more rational strategies based on genetic manipulations and heterologous expression in optimized chassis. Recent construction of various genetically modified strains of Streptomyces lividans has shown their use for efficient heterologous production of various biologically active secondary metabolites including MTM. KEY POINTS: • Discovery a novel bifunctional glycosyl hydrolase from uncultured microorganism. • Heterologous production of MTM in engineered S. lividans strains is efficient.
Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Humans; Plicamycin; Polyketides; Sarcoma, Ewing
PubMed: 32686008
DOI: 10.1007/s00253-020-10782-x