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Respirology (Carlton, Vic.) Aug 2019
Topics: Adrenal Cortex Hormones; Cyclophosphamide; Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Propensity Score
PubMed: 31212393
DOI: 10.1111/resp.13621 -
Cancer Jan 2022Sarculator is better at predicting patients with sarcoma at the highest risk of death than current staging systems and should be used to determine appropriate patients...
Sarculator is better at predicting patients with sarcoma at the highest risk of death than current staging systems and should be used to determine appropriate patients for future studies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Ifosfamide; Sarcoma; Soft Tissue Neoplasms
PubMed: 34643940
DOI: 10.1002/cncr.33896 -
Chemico-biological Interactions Dec 2021Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents... (Review)
Review
Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents occurred not only due to their use as chemical warfare agents but also because of occupational hazards. Therefore, a clear understanding of these agents and their mode of action is essential to develop effective decontamination and therapeutic strategies. The blister agents have been categorised on the basis of their chemistry and the biological interactions that entail post contamination. These compounds have been known to majorly cause blisters/bullae along with alkylation of the contaminated DNA. However, due to the high toxicity and restricted use, very little research has been conducted and a lot remains to be clearly understood about these compounds. Various decontamination solutions and detection technologies have been developed, which have proven to be effective for their timely mitigation. But a major hurdle seems to be the lack of proper understanding of the toxicological mechanism of action of these compounds. Current review is about the detailed and updated information on physical, chemical and biological aspects of various blister agents. It also illustrates the mechanism of their action, toxicological effects, detection technologies and possible decontamination strategies.
Topics: Alkylating Agents; Arsenicals; Blister; Chemical Warfare Agents; Decontamination; Eye; Humans; Lung; Models, Biological; Mustard Compounds; Oximes; Phosgene; Skin
PubMed: 34634268
DOI: 10.1016/j.cbi.2021.109654 -
Oncology Reports Jun 2022Bendamustine is an alkylating agent classified into the group of nitrogen mustard analogues, synthesized almost sixty years ago. It was registered in former East Germany... (Review)
Review
Bendamustine is an alkylating agent classified into the group of nitrogen mustard analogues, synthesized almost sixty years ago. It was registered in former East Germany in 1971 and approved by the US Food and Drug Administration in 2008 for treatment of chronic lymphocytic leukemia and indolent B‑cell non‑Hodgkin lymphoma. Considering its beneficial properties in the therapy of relapsed or refractory hematological malignancies, synergistic effects with other antineoplastic agents and increasing recent reports on its immunomodulatory effects, bendamustine has once again gained its justified attention. The uniqueness of bendamustine‑mediated effects should be observed keeping in mind its distinctive structure with structural similarities to both alkylating agents and purine analogs. In the present review, the current knowledge on the use of bendamustine in oncology, its pharmacokinetics, mechanism of action and toxicity was summarized. In addition, its immune‑modulating effects that have not been fully elucidated so far are emphasized, hoping to encourage further investigations of this unique drug.
Topics: Antineoplastic Agents; Bendamustine Hydrochloride; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Nitrogen Mustard Compounds
PubMed: 35506458
DOI: 10.3892/or.2022.8325 -
Cancer Sep 2019
Topics: Child; Cyclophosphamide; Humans; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal
PubMed: 31174230
DOI: 10.1002/cncr.32205 -
Environmental Science and Pollution... Oct 2021Chemical warfare (CW) agents are toxic synthetic chemicals that affect human's health, and sulfur mustard (SM) is a well-known chemical weapon that caused deaths of... (Review)
Review
Chemical warfare (CW) agents are toxic synthetic chemicals that affect human's health, and sulfur mustard (SM) is a well-known chemical weapon that caused deaths of victims. The lung is the main target of SM exposure, and there are no definitive therapeutic modalities for lung injury induced by this agent. The possible therapeutic effects of medicinal plants and their active ingredients on lung injury induced by SM were reviewed in this article until the end of June 2021. Medicinal plants including Crocus sativus, Curcuma longa, Thymus vulgaris, Nigella sativa, and Zataria multiflora and also natural compounds showed therapeutic potential in improving of various features of lung injury induced by SM and other related chemical agents. Several studies showed therapeutic effects of some medicinal plants and natural products on lung inflammation, oxidative stress, and immune responses in experimental studies in SM-induced lung injury. In addition, clinical studies also showed the effect of medicinal plants and natural compounds on respiratory symptoms, pulmonary function tests (PFTs), and inflammatory markers. The therapeutic effects of medicinal plants and natural products on lung disorder induced by SM and related chemical agents were shown through amelioration of various features of lung injury.
Topics: Humans; Lung; Mustard Gas; Plants, Medicinal
PubMed: 34382165
DOI: 10.1007/s11356-021-15697-2 -
Expert Review of Clinical Pharmacology Apr 2022Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that takes advantage of increased aminopeptidase activity inside tumor cells to rapidly...
INTRODUCTION
Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that takes advantage of increased aminopeptidase activity inside tumor cells to rapidly release alkylating agents therein. Melflufen in combination with dexamethasone has been evaluated in multiple clinical trials in patients with relapsed/refractory multiple myeloma (MM).
AREAS COVERED
This profile covers the unique mechanism of action of melflufen, the preclinical results supporting its activity in cellular models of resistance to chemotherapy, its activity in animal models of MM, and the clinical pharmacokinetics of melflufen. Findings from clinical trials evaluating melflufen, including the pivotal phase II HORIZON study and the phase III OCEAN study, are discussed.
EXPERT OPINION
Although MM treatment has improved, patients with disease refractory to multiple standard-of-care drug classes face a dismal prognosis. Melflufen demonstrated efficacy and tolerability in select populations, with an initial approval in the United States in patients with ≥ four previous lines of therapy and triple-class-refractory MM. Results from the phase III OCEAN study - currently under discussion with regulatory agencies in the United States and Europe - are more complex and have been put into context herein. Lastly, melflufen provides a proof-of-concept for the utility of the peptide-drug conjugate platform in relapsed/refractory MM.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Europe; Melphalan; Multiple Myeloma; Phenylalanine
PubMed: 35723075
DOI: 10.1080/17512433.2022.2075847 -
Advances in Health Sciences Education :... Dec 2022Professionals will increasingly be confronted with new insights and changes. This raises questions as to what kind of expertise professionals need, and how development... (Review)
Review
Professionals will increasingly be confronted with new insights and changes. This raises questions as to what kind of expertise professionals need, and how development of this expertise can be influenced within the contexts of both education and work. The terms adaptive expertise and adaptive performance are well-known concepts in the domains of education and Human Resource Development respectively. The literature, however, lacks a conceptual overview. Our research seeks to provide an overview on how adaptive expertise and adaptive performance are conceptualized. In addition we looked for what individual, task and organizational characteristics relate to adaptive expertise. We mined information drawn from existing reviews in an overview of reviews. Nine reviews met the inclusion criteria. Adaptive performance is best referred to as the visible expression of an adaptive expert and this is triggered by 'change'. The scope of this 'change' lies somewhere between change that is 'new for the learner' and change that is 'new for everyone in the whole world'. The extent to and way in which a learner or professional is able to deal with this change depends on the maturity of the learner or professional. We found numerous individual, task and environmental characteristics related to adaptive expertise and adaptive performance. The nature and relation of these characteristics, and their specificity in relation to adaptive expertise and adaptive performance are visualized in a figure, but also provide several suggestions for future research.
Topics: Humans; Educational Status; Workplace; Clinical Competence; Etoposide; Ifosfamide
PubMed: 36508136
DOI: 10.1007/s10459-022-10190-y -
Hematological Oncology Oct 2023We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were... (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of immunochemotherapy with R-bendamustine or R-CHOP for treatment naïve advanced-stage follicular lymphoma: A subset analysis of the FOLL12 trial by Fondazione Italiana Linfomi.
We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were selected from the FOLL12 trial, which included adults with stage II-IV follicular lymphoma (FL) grade 1-3a and high tumor burden. Patients were randomized 1:1 to receive either standard ICT followed by rituximab maintenance (RM) or the same ICT followed by a response-adapted approach. ICT consisted of rituximab-bendamustine (RB) or rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP), per physician's decision. A total of 786 patients were included in this analysis, 341 of whom received RB and 445 R-CHOP. RB was more frequently prescribed to older subjects, females, patients without bulky disease, and those with grade 1-2 FL. After a median of 56 months of follow-up, R-CHOP and RB had similar progression-free survival (PFS) (Hazard Ratio for RB 1.11, 95% CI 0.87-1.42, p = 0.392). Standard RM was associated with improved PFS compared to response-adapted management both after R-CHOP and RB. Grade 3-4 hematologic adverse events were more frequent with R-CHOP during induction treatment and more frequent with RB during RM. Grade 3-4 infections were more frequent with RB. RB was also associated with a higher incidence of transformed FL. R-CHOP and RB showed similar activity and efficacy, but with different safety profiles and long-term events, suggesting that the treating physician should carefully select the most appropriate chemotherapy regimen for each patient based on patient's individual characteristics, choices, and risk profile.
Topics: Adult; Female; Humans; Rituximab; Bendamustine Hydrochloride; Lymphoma, Follicular; Prednisone; Neoplasm Recurrence, Local; Vincristine; Cyclophosphamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37246287
DOI: 10.1002/hon.3184 -
Hereditas Mar 2023Systemic lupus erythematosus (SLE) is an autoimmune disorder which could lead to inflammation and fibrosis in various organs. Pulmonary fibrosis is a severe complication...
BACKGROUND
Systemic lupus erythematosus (SLE) is an autoimmune disorder which could lead to inflammation and fibrosis in various organs. Pulmonary fibrosis is a severe complication in patients with SLE. Nonetheless, SLE-derived pulmonary fibrosis has unknown pathogenesis. Of pulmonary fibrosis, Idiopathic pulmonary fibrosis (IPF) is a typicality and deadly form. Aiming to investigate the gene signatures and possible immune mechanisms in SLE-derived pulmonary fibrosis, we explored common characters between SLE and IPF from Gene Expression Omnibus (GEO) database.
RESULTS
We employed the weighted gene co-expression network analysis (WGCNA) to identify the shared genes. Two modules were significantly identified in both SLE and IPF, respectively. The overlapped 40 genes were selected out for further analysis. The GO enrichment analysis of shared genes between SLE and IPF was performed with ClueGO and indicated that p38MAPK cascade, a key inflammation response pathway, may be a common feature in both SLE and IPF. The validation datasets also illustrated this point. The enrichment analysis of common miRNAs was obtained from the Human microRNA Disease Database (HMDD) and the enrichment analysis with the DIANA tools also indicated that MAPK pathways' role in the pathogenesis of SLE and IPF. The target genes of these common miRNAs were identified by the TargetScan7.2 and a common miRNAs-mRNAs network was constructed with the overlapped genes in target and shared genes to show the regulated target of SLE-derived pulmonary fibrosis. The result of CIBERSORT showed decreased regulatory T cells (Tregs), naïve CD4+ T cells and rest mast cells but increased activated NK cells and activated mast cells in both SLE and IPF. The target genes of cyclophosphamide were also obtained from the Drug Repurposing Hub and had an interaction with the common gene PTGS2 predicted with protein-protein interaction (PPI) and molecular docking, indicating its potential treatment effect.
CONCLUSIONS
This study originally uncovered the MAPK pathway, and the infiltration of some immune-cell subsets might be pivotal factors for pulmonary fibrosis complication in SLE, which could be used as potentially therapeutic targets. The cyclophosphamide may treat SLE-derived pulmonary fibrosis through interaction with PTGS2, which could be activated by p38MAPK.
Topics: Humans; Cyclooxygenase 2; Molecular Docking Simulation; Idiopathic Pulmonary Fibrosis; MicroRNAs; Lupus Erythematosus, Systemic; Inflammation; Cyclophosphamide
PubMed: 36871016
DOI: 10.1186/s41065-023-00270-3