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Dermatology Online Journal Dec 2013A 21-year-old woman presented with a pruritic eruption on her trunk and extremities after receiving bleomycin for treatment of stage III ovarian germ-cell tumor....
A 21-year-old woman presented with a pruritic eruption on her trunk and extremities after receiving bleomycin for treatment of stage III ovarian germ-cell tumor. Physical examination was consistent with bleomycin-induced flagellate erythema. We discuss the pathophysiologic mechanism that produces this dermatitis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Drug Eruptions; Erythema; Etoposide; Female; Humans; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Young Adult
PubMed: 24365007
DOI: No ID Found -
Advanced Drug Delivery Reviews Jan 2024Pulmonary fibrosis (PF) is a progressive, and life-threatening interstitial lung disease which causes scarring in the lung parenchyma and thereby affects architecture... (Review)
Review
Pulmonary fibrosis (PF) is a progressive, and life-threatening interstitial lung disease which causes scarring in the lung parenchyma and thereby affects architecture and functioning of lung. It is an irreversible damage to lung functioning which is related to epithelial cell injury, immense accumulation of immune cells and inflammatory cytokines, and irregular recruitment of extracellular matrix. The inflammatory cytokines trigger the differentiation of fibroblasts into activated fibroblasts, also known as myofibroblasts, which further increase the production and deposition of collagen at the injury sites in the lung. Despite the significant morbidity and mortality associated with PF, there is no available treatment that efficiently and effectively treats the disease by reversing their underlying pathologies. In recent years, many therapeutic regimens, for instance, rho kinase inhibitors, Smad signaling pathway inhibitors, p38, BCL-xL/ BCL-2 and JNK pathway inhibitors, have been found to be potent and effective in treating PF, in preclinical stages. However, due to non-selectivity and non-specificity, the therapeutic molecules also result in toxicity mediated severe side effects. Hence, this review demonstrates recent advances on PF pathology, mechanism and targets related to PF, development of various drug delivery systems based on small molecules, RNAs, oligonucleotides, peptides, antibodies, exosomes, and stem cells for the treatment of PF and the progress of various therapeutic treatments in clinical trials to advance PF treatment.
Topics: Humans; Pulmonary Fibrosis; Bleomycin; Fibrosis; Lung; Cytokines
PubMed: 38065244
DOI: 10.1016/j.addr.2023.115147 -
Brazilian Journal of Otorhinolaryngology 2023At present, bleomycin has been widely used in the treatment of Lymphatic Malformations (LMs). This study aims to perform a meta-analysis to investigate the effectiveness... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
At present, bleomycin has been widely used in the treatment of Lymphatic Malformations (LMs). This study aims to perform a meta-analysis to investigate the effectiveness and influencing factors of bleomycin in the treatment of LMs.
METHODS
We conducted a systematic review and meta-analysis to clarify the relationship between bleomycin and LMs. PubMed, ISI Web of Science and MEDLINE were searched.
RESULTS
A total of 21 studies (including 428 cases) about bleomycin sclerotherapy for LMs were included in the current meta-analyses. We calculated pooled effective rate and 95% Confidence Interval (95% CI) using random effects model to evaluate the relations between bleomycin and LMs. The results suggested that the effective rate of bleomycin was the combined effective rate was 84.0% (95% CI 0.81‒0.87) and ranged from 39% (95% CI 0.22‒0.56) to 94% (95% CI 0.87-1.02). The heterogeneity among the studies was substantial (I=61.7%, p= 0.000). In subgroup analyses, it was observed that among retrospective study and prospective study, the estimated effective rate was 80.0% (95% CI 0.76‒0.84) and 91.0% (95% CI 0.85‒0.97), respectively. In terms of the dosage, the combined effective rates of weight-based group and fixed-dose group were 86% (95% CI 0.83‒0.90) and 74.0% (95% CI 0.66‒0.82), respectively. There was no significant publication bias in Egger's test (p=0.059, 95% CI -3.81 to 0.082), but Begg's test did (p=0.023), and the funnel plot is asymmetric.
CONCLUSION
Our study suggested that bleomycin was safe and effective in the treatment of LMs and was primarily dose dependent.
Topics: Humans; Sclerotherapy; Bleomycin; Retrospective Studies; Prospective Studies; Treatment Outcome; Lymphatic Abnormalities
PubMed: 37423005
DOI: 10.1016/j.bjorl.2023.101285 -
Interventional Neuroradiology : Journal... Apr 2021Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such...
BACKGROUND
Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such malformations.
OBJECTIVE
The purpose of this systematic review is to synthesize evidence on the safety and efficacy of bleomycin/pingyangmycin sclerotherapy for the treatment of orbital and peri-orbital VLM.
METHODS
We searched Medline, Embase, Scopus and Cochrane database for studies reporting outcomes of bleomycin/pingyangmycin sclerotherapy for orbital and peri-orbital VLM between 1974 to April 5th, 2019. Nine retrospective cohort studies enrolling 132 patients were included. Two reviewers independently screened and extracted data and assessed the risk of bias. Predefined outcome measures were subjective and objective reduction of the lesion and associated complications.
RESULTS
Subjective reduction of the lesions was seen in 96.2% of the studies. Objective reduction of the lesion and symptomatic improvement were reported in 91.6 and 95% of the studies respectively. Non responders were 9.0%. Minor adverse events were reported in 18.1% of the studies. Major complications like pulmonary toxicity or pulmonary fibrosis was not encountered in any of the included studies. Quality of evidence was generally low.
CONCLUSION
Bleomycin/pingyangmycin sclerotherapy is very effective and relatively safe for the treatment of orbital and periorbital VLM and is not associated with any major side effects including pulmonary fibrosis. The systematic review is limited mainly due to low quality of the included studies with retrospective design.
Topics: Bleomycin; Humans; Injections, Intralesional; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome; Vascular Malformations
PubMed: 33175616
DOI: 10.1177/1591019920972514 -
Stem Cells Translational Medicine May 2016This authors’ reply to a letter to the editor addresses whether young rodents are appropriate animal models for advanced-age human disease.
This authors’ reply to a letter to the editor addresses whether young rodents are appropriate animal models for advanced-age human disease.
Topics: Animals; Bleomycin; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pulmonary Fibrosis
PubMed: 27091589
DOI: 10.5966/sctm.2015-0406 -
Scientific Reports Sep 2023Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF,...
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3-5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.
Topics: Animals; Mice; PPAR gamma; Lignans; Idiopathic Pulmonary Fibrosis; Bleomycin
PubMed: 37679587
DOI: 10.1038/s41598-023-41933-5 -
American Journal of Respiratory Cell... Jul 2023VISTA (V domain immunoglobulin suppressor of T cell activation, also called PD-1H [programmed death-1 homolog]), a novel immune regulator expressed on myeloid and T...
VISTA (V domain immunoglobulin suppressor of T cell activation, also called PD-1H [programmed death-1 homolog]), a novel immune regulator expressed on myeloid and T lymphocyte lineages, is upregulated in mouse and human idiopathic pulmonary fibrosis (IPF). However, the significance of VISTA and its therapeutic potential in regulating IPF has yet to be defined. To determine the role of VISTA and its therapeutic potential in IPF, the expression profile of VISTA was evaluated from human single-cell RNA sequencing data (IPF Cell Atlas). Inflammatory response and lung fibrosis were assessed in bleomycin-induced experimental pulmonary fibrosis models in VISTA-deficient mice compared with wild-type littermates. In addition, these outcomes were evaluated after VISTA agonistic antibody treatment in the wild-type pulmonary fibrosis mice. VISTA expression was increased in lung tissue-infiltrating monocytes of patients with IPF. VISTA was induced in the myeloid population, mainly circulating monocyte-derived macrophages, during bleomycin-induced pulmonary fibrosis. Genetic ablation of VISTA drastically promoted pulmonary fibrosis, and bleomycin-induced fibroblast activation was dependent on the interaction between VISTA-expressing myeloid cells and fibroblasts. Treatment with VISTA agonistic antibody reduced fibrotic phenotypes accompanied by the suppression of lung innate immune and fibrotic mediators. In conclusion, these results suggest that VISTA upregulation in pulmonary fibrosis may be a compensatory mechanism to limit inflammation and fibrosis, and stimulation of VISTA signaling using VISTA agonists effectively limits the fibrotic innate immune landscape and consequent tissue fibrosis. Further studies are warranted to test VISTA as a novel therapeutic target for the IPF treatment.
Topics: Humans; Mice; Animals; Idiopathic Pulmonary Fibrosis; Lung; Fibrosis; Bleomycin; Inflammation; Fibroblasts
PubMed: 36450109
DOI: 10.1165/rcmb.2022-0219OC -
American Journal of Respiratory Cell... May 2022
Topics: Bleomycin; Humans; Myofibroblasts; Pulmonary Fibrosis; p38 Mitogen-Activated Protein Kinases
PubMed: 35238730
DOI: 10.1165/rcmb.2022-0026ED -
Translational Research : the Journal of... Mar 2023Ubiquitination-mediated protein degradation is associated with the development of pulmonary fibrosis. We and others have shown that Nedd4L plays anti-inflammatory and...
Ubiquitination-mediated protein degradation is associated with the development of pulmonary fibrosis. We and others have shown that Nedd4L plays anti-inflammatory and anti-fibrotic roles by targeting lysophosphatidic acid receptor 1 (LPAR1), p-Smad2/3, and β-catenin, and other molecules for their degradation in lung epithelial cells and fibroblasts. However, the molecular regulation of Nedd4L expression in lung fibroblasts has not been studied. In this study, we find that Nedd4L levels are significantly suppressed in lung myofibroblasts in IPF patients and in experimental pulmonary fibrosis, and in TGF-β1-treated lung fibroblasts. Nedd4L knockdown promotes TGF-β1-mediated phosphorylation of Smad2/3 and lung myofibroblast differentiation. Mechanistically, Nedd4L targets TGF-β receptor II (TβRII), the first key enzyme of TGF-β1-mediated signaling, for its ubiquitination and degradation. Further, we show that inhibition of transcriptional factor E2F rescues Nedd4L levels and mitigates experimental pulmonary fibrosis. Together, our data reveal insight into mechanisms by which E2F-mediated Nedd4L suppression contributes to the pathogenesis of lung fibrosis. This study provides evidence showing that upregulation of Nedd4L is a potential therapeutic strategy to treat fibrotic disorders including lung fibrosis.
Topics: Humans; Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung; Fibroblasts; Cell Differentiation; Myofibroblasts; Fibrosis; Bleomycin
PubMed: 36257596
DOI: 10.1016/j.trsl.2022.10.002 -
GeroScience Apr 2024As we age, the ability to regenerate and repair skeletal muscle damage declines, partially due to increasing dysfunction of muscle resident stem cells-satellite cells...
As we age, the ability to regenerate and repair skeletal muscle damage declines, partially due to increasing dysfunction of muscle resident stem cells-satellite cells (SC). Recent evidence implicates cellular senescence, which is the irreversible arrest of proliferation, as a potentiator of SC impairment during aging. However, little is known about the role of senescence in SC, and there is a large discrepancy in senescence classification within skeletal muscle. The purpose of this study was to develop a model of senescence in skeletal muscle myoblasts and identify how common senescence-associated biomarkers respond. Low-passage CC myoblasts were treated with bleomycin or vehicle and then evaluated for cytological and molecular senescence markers, proliferation status, cell cycle kinetics, and differentiation potential. Bleomycin treatment caused double-stranded DNA breaks, which upregulated p21 mRNA and protein, potentially through NF-κB and senescence-associated super enhancer (SASE) signaling (p < 0.01). Consequently, cell proliferation was abruptly halted due to G2/M-phase arrest (p < 0.01). Bleomycin-treated myoblasts displayed greater senescence-associated β-galactosidase staining (p < 0.01), which increased over several days. These myoblasts remained senescent following 6 days of differentiation and had significant impairments in myotube formation (p < 0.01). Furthermore, our results show that senescence can be maintained despite the lack of p16 gene expression in CC myoblasts. In conclusion, bleomycin treatment provides a valid model of damage-induced senescence that was associated with elevated p21, reduced myoblast proliferation, and aberrant cell cycle kinetics, while confirming that a multi-marker approach is needed for the accurate classification of senescence within skeletal muscle.
Topics: Bleomycin; Cell Line; Cellular Senescence; Cell Differentiation; Myoblasts; Biomarkers
PubMed: 37751045
DOI: 10.1007/s11357-023-00929-9