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Ugeskrift For Laeger Aug 2015Cutaneous metastases occur in up to 9% of all patients with cancer and may cause discomfort and stigmatization. Electrochemotherapy is a local treatment using electric... (Review)
Review
Cutaneous metastases occur in up to 9% of all patients with cancer and may cause discomfort and stigmatization. Electrochemotherapy is a local treatment using electric pulses to permeabilize cell membranes, enabling chemotherapy, such as bleomycin, to enter the cells and increase the cytotoxic effect by at least 300-fold. Electrochemotherapy is an efficient, once only treatment for cutaneous metastases with an objective response of 62-99%. Electrochemotherapy can reduce discomfort such as ulceration, oozing, bleeding and pain. Adverse events depend on the size of treatment area, but are very limited.
Topics: Antibiotics, Antineoplastic; Bleomycin; Electrochemotherapy; Humans; Neoplasm Metastasis; Skin Neoplasms
PubMed: 26321586
DOI: No ID Found -
Indian Pediatrics Feb 2015
Topics: Antibiotics, Antineoplastic; Bleomycin; Child, Preschool; Humans; Injections, Intralesional; Lymphangioma; Male; Tongue
PubMed: 25691206
DOI: 10.1007/s13312-015-0602-5 -
Cells Dec 2022DNA damage is the major cause of senescence and apoptosis; however, the manner by which DNA-damaged cells become senescent remains unclear. We demonstrate that DNA...
DNA damage is the major cause of senescence and apoptosis; however, the manner by which DNA-damaged cells become senescent remains unclear. We demonstrate that DNA damage leads to a greater level of senescence rather than apoptosis in DBC1-deficient cells. In addition, we show that BLM becomes degraded during DNA damage, which induces p21 expression and senescence. DBC1 binds to and shields BLM from degradation, thus suppressing senescence. ML216 promotes DBC1-BLM interaction, which aids in the preservation of BLM following DNA damage and suppresses senescence. ML216 enhances pulmonary function by lowering the levels of senescence and fibrosis in both aged mice and a mouse model of bleomycin-induced idiopathic pulmonary fibrosis. Our data reveal a unique mechanism preventing DNA-damaged cells from becoming senescent, which may be regulated by the use of ML216 as a potential treatment for senescence-related diseases.
Topics: Animals; Mice; Bleomycin; DNA; DNA Damage; DNA Helicases; Idiopathic Pulmonary Fibrosis; Lung
PubMed: 36611939
DOI: 10.3390/cells12010145 -
Scientific Reports May 2020The concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. Microbubble sonodestruction dynamics and cavitation...
The concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. Microbubble sonodestruction dynamics and cavitation spectral characteristics, ultrasound scattering and attenuation, were examined in relation to the intracellular delivery of anticancer drug, bleomycin. Experiments were conducted on Chinese hamster ovary cells coadministered with Sonovue microbubbles. Detailed analysis of the scattering and attenuation temporal functions culminated in quantification of metrics, inertial cavitation dose and attenuation rate, suitable for cavitation control. The exponents, representing microbubble sonodestruction kinetics were exploited to derive dosimetric, microbubble sonodestruction rate. High intracorrelation between empirically-attained metrics defines the relations which indicate deep physical interdependencies within inherent phenomena. Subsequently each quantified metric was validated to be well-applicable to prognosticate the efficacy of bleomycin delivery and cell viability, as indicated by strong overall correlation (R > 0.85). Presented results draw valuable insights in sonoporation dosimetry and contribute towards the development of universal sonoporation dosimetry model. Both bleomycin delivery and cell viability reach their respective plateau levels by the time, required to attain total microbubble sonodestruction, which accord with scattering and attenuation decrease to background levels. This suggests a well-defined criterion, feasible through signal-registration, universally employable to set optimal duration of exposure for efficient sonoporation outcome.
Topics: Bleomycin; Drug Delivery Systems; Microbubbles; Ultrasonic Waves
PubMed: 32385397
DOI: 10.1038/s41598-020-64213-y -
British Journal of Cancer Oct 2018Bleomycin, a cytotoxic chemotherapy agent, forms a key component of curative regimens for lymphoma and germ cell tumours. It can be associated with severe toxicity,... (Review)
Review
Bleomycin, a cytotoxic chemotherapy agent, forms a key component of curative regimens for lymphoma and germ cell tumours. It can be associated with severe toxicity, long-term complications and even death in extreme cases. There is a lack of evidence or consensus on how to prevent and monitor bleomycin toxicity. We surveyed 63 germ cell cancer physicians from 32 cancer centres across the UK to understand their approach to using bleomycin. Subsequent guideline development was based upon current practice, best available published evidence and expert consensus. We observed heterogeneity in practice in the following areas: monitoring; route of administration; contraindications to use; baseline and follow-up investigations performed, and advice given to patients. A best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours has been developed and includes recommendations regarding baseline investigations, the use of pulmonary function tests, route of administration, monitoring and patient advice. It is likely that existing heterogeneity in clinical practice of bleomycin prescribing has significant economic, safety and patient experience implications. The development of an evidence-based consensus guideline was supported by 93% of survey participants and aims to address these issues and homogenise practice across the UK.
Topics: Antibiotics, Antineoplastic; Bleomycin; Clinical Trials as Topic; Consensus; Evidence-Based Medicine; Humans; Male; Neoplasms, Germ Cell and Embryonal; Respiratory Function Tests; Testicular Neoplasms; United Kingdom
PubMed: 30356125
DOI: 10.1038/s41416-018-0300-x -
Cell Death & Disease Nov 2020It is of clinical importance to identify biomarkers predicting the efficacy of DNA damaging drugs (genotoxins) so that nonresponders are not unduly exposed to the...
It is of clinical importance to identify biomarkers predicting the efficacy of DNA damaging drugs (genotoxins) so that nonresponders are not unduly exposed to the deleterious effects of otherwise inefficient drugs. Here, we initially focused on the bleomycin genotoxin because of the limited information about the genes implicated in the sensitivity or resistance to this compound. Using a whole-genome CRISPR/Cas9 gene knockout approach, we identified ASH2L, a core component of the H3K4 methyl transferase complex, as a protein required for bleomycin sensitivity in L1236 Hodgkin lymphoma. Knocking down ASH2L in these cells and in the NT2D1 testicular cancer cell line rendered them resistant to bleomycin, etoposide, and cisplatin but did not affect their sensitivity toward ATM or ATR inhibitors. ASH2L knockdown decreased cell proliferation and facilitated DNA repair via homologous recombination and nonhomologous end-joining mechanisms. Data from the Tumor Cancer Genome Atlas indicate that patients with testicular cancer carrying alterations in the ASH2L gene are more likely to relapse than patients with unaltered ASH2L genes. The cell models we have used are derived from cancers currently treated either partially (Hodgkin's lymphoma), or entirely (testicular cancer) with genotoxins. For such cancers, ASH2L levels could be used as a biomarker to predict the response to genotoxins. In situations where tumors are expressing low levels of ASH2L, which may allow them to resist genotoxic treatment, the use of ATR or ATM inhibitors may be more efficacious as our data indicate that ASH2L knockdown does not affect sensitivity to these inhibitors.
Topics: Bleomycin; Cell Proliferation; DNA-Binding Proteins; Female; Hodgkin Disease; Humans; Male; Nuclear Proteins; Testicular Neoplasms; Transcription Factors
PubMed: 33257682
DOI: 10.1038/s41419-020-03231-0 -
Journal of Natural Products Mar 2011The biosynthetic gene clusters for the glycopeptide antitumor antibiotics bleomycin (BLM), tallysomycin (TLM), and zorbamycin (ZBM) have been recently cloned and... (Review)
Review
The biosynthetic gene clusters for the glycopeptide antitumor antibiotics bleomycin (BLM), tallysomycin (TLM), and zorbamycin (ZBM) have been recently cloned and characterized from Streptomyces verticillus ATCC15003, Streptoalloteichus hindustanus E465-94 ATCC31158, and Streptomyces flavoviridis ATCC21892, respectively. The striking similarities and differences among the biosynthetic gene clusters for the three structurally related glycopeptide antitumor antibiotics prompted us to compare and contrast their respective biosynthetic pathways and to investigate various enzymatic elements. The presence of different numbers of isolated nonribosomal peptide synthetase (NRPS) domains in all three clusters does not result in major structural differences of the respective compounds. The seemingly identical domain organization of the NRPS modules responsible for heterocycle formation, on the other hand, is contrasted by the biosynthesis of two different structural entities, bithiazole and thiazolinyl-thiazole, for BLM/TLM and ZBM, respectively. Variations in sugar biosynthesis apparently dictate the glycosylation patterns distinct for each of the BLM, TLM, and ZBM glycopeptide scaffolds. These observations demonstrate nature's ingenuity and flexibility in achieving structural differences and similarities via various mechanisms and will surely inspire combinatorial biosynthesis efforts to expand on natural product structural diversity.
Topics: Antibiotics, Antineoplastic; Biological Products; Bleomycin; Glycopeptides; Multigene Family; Peptide Synthases
PubMed: 21210656
DOI: 10.1021/np1008152 -
Molecules (Basel, Switzerland) Oct 2021One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some...
One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some similarities with radiation therapy, one of which could be the bystander effect. In this study, we aimed to investigate the role of the bystander effect following these electroporation-based treatments. During direct CHO-K1 cell treatment, cells were electroporated using one 100 µs duration square wave electric pulse at 1400 V/cm (for bleomycin electrotransfer) or 2800 V/cm (for irreversible electroporation). To evaluate the bystander effect, the medium was taken from directly treated cells after 24 h incubation and applied on unaffected cells. Six days after the treatment, cell viability and colony sizes were evaluated using the cell colony formation assay. The results showed that the bystander effect after bleomycin electrotransfer had a strong negative impact on cell viability and cell colony size, which decreased to 2.8% and 23.1%, respectively. On the contrary, irreversible electroporation induced a strong positive bystander effect on cell viability, which increased to 149.3%. In conclusion, the results presented may serve as a platform for further analysis of the bystander effect after electroporation-based therapies and may ultimately lead to refined application of these therapies in clinics.
Topics: Alarmins; Animals; Bleomycin; Bystander Effect; CHO Cells; Cell Survival; Cricetulus; Electrochemotherapy; Electroporation; Reactive Oxygen Species
PubMed: 34641546
DOI: 10.3390/molecules26196001 -
Indian Journal of Dermatology,... 2019This study evaluated the efficacy and safety of intralesional bleomycin in the treatment of common warts in 50 (32 men, 18 women) patients aged between 14 and 80 (mean...
BACKGROUND
This study evaluated the efficacy and safety of intralesional bleomycin in the treatment of common warts in 50 (32 men, 18 women) patients aged between 14 and 80 (mean ± SD, 28.5 ± 13.27) years.
METHODS
The warts were present over dorsal hands, feet, palms, soles and periungual skin for 1 month to 10 years. They were infiltrated with bleomycin (1 mg/ml) till blanching. The total cumulative dose did not exceed 2 mg in one session. The treatment was repeated after paring of eschar at 2 weeks in case there was no or partial response. The patients were reviewed at 4, 12 and 24 weeks for cure, adverse effects or recurrences and outcome satisfaction levels.
RESULTS
Complete cure without recurrence occurred in 40 (80%) patients and partial response occurred in 7 (14%) patients at the end of the 24-week study period. Three patients did not complete follow-up. No major systemic or local adverse effects other than injection site pain for 2-3 days were noted. All cured patients were very satisfied (Likert scale 5).
CONCLUSION
Intralesional bleomycin appears to be an effective and safe treatment for common warts including palmoplantar and periungual warts. It carries the advantage of low dose, no significant adverse effects and high patient satisfaction. Small number of patients, lack of a control group, comparing different bleomycin concentrations and a short follow-up are a few limitations of this study. Better designed studies are warranted for this useful treatment modality.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Bleomycin; Female; Humans; Injection Site Reaction; Injections, Intralesional; Male; Middle Aged; Pain; Pilot Projects; Recurrence; Warts; Young Adult
PubMed: 29956682
DOI: 10.4103/ijdvl.IJDVL_519_17 -
Chembiochem : a European Journal of... Jan 2018Noncoding RNAs are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is whether noncoding RNAs are targets of medicines....
Noncoding RNAs are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is whether noncoding RNAs are targets of medicines. Bleomycin is a natural product that cleaves DNA; however, it is known to cleave RNA in vitro. Herein, an in-depth analysis of the RNA cleavage preferences of bleomycin A5 is presented. Bleomycin A5 prefers to cleave RNAs with stretches of AU base pairs. Based on these preferences and bioinformatic analysis, the microRNA-10b hairpin precursor was identified as a potential substrate for bleomycin A5. Both in vitro and cellular experiments demonstrated cleavage. Importantly, chemical cleavage by bleomycin A5 in the microRNA-10b hairpin precursors occurred near the Drosha and Dicer enzymatic processing sites and led to destruction of the microRNA. Evidently, oncogenic noncoding RNAs can be considered targets of cancer medicines and might elicit their pharmacological effects by targeting noncoding RNA.
Topics: Base Sequence; Bleomycin; HeLa Cells; Humans; MicroRNAs; Nucleic Acid Conformation; RNA Cleavage; RNA, Untranslated; Ribonuclease III
PubMed: 29084369
DOI: 10.1002/cbic.201700581