Revisiting bleomycin from pathophysiology to safe clinical use

Froudarakis, Marios; Hatzimichael, Eleftheria; Kyriazopoulou, Lydia; Lagos, Konstantinos; Pappas, Periklis; Tzakos, Andreas G.; Karavasilis, Vasilios; Daliani, Danai; Papandreou, Christos N.; Briasoulis, Evangelos

doi:10.1016/j.critrevonc.2012.12.003

Cited by 99 publications

(65 citation statements)

References 74 publications

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“…Bleomycin‐induced adverse effects include GI disorders, myelosuppression, cutaneous reactions, and pulmonary toxicity, in particular severe and life‐threatening lung fibrosis (Froudarakis et al. 2013; Della Latta et al. 2015).…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

194

161

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

194

161

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“…Bleomycin (BLM) is anti-tumor antibiotic glycopeptide produced by actinobacterium Streptomyces verticillu [4]. Cytotoxic activity of BLM is through oxidation in deoxyribose of thymidylate and other nucleotides, which produced single-strand and double-strand breaks in DNA, chromosomal aberration, gaps, fragments and translocation [4].…”

Section: Introductionmentioning

confidence: 99%

Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway

Liu

Nie

Shao

et al. 2016

Cell Physiol Biochem

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Background/Aims:Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single-and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. Methods: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). Results: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. Conclusion: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients.

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“…6,15,16 A bleomicina resulta em um distúrbio restritivo associado a redução da difusão de monóxido de carbono, CPT, capacidade vital e do VEF1 em cerca de 50% dos casos. 17,18 A toxicidade pulmonar pela bleomicina é na maioria das vezes advinda das doses acumulativas, tendo sido evidenciado que doses inferiores a 300 mg raramente causam toxicidade pulmonar e à medida que a dose excede 400 mg há risco de desenvolvimento de toxicidade. …”

Section: Discussionunclassified

Avaliação da função pulmonar em pacientes com câncer submetidos à quimioterapia

Vione

Wagner

Benelli

et al. 2016

Rev Epidemiol Control Infect

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Avaliação da função pulmonar em pacientes com câncer submetidos à quimioterapia Evaluation of the lung function in cancer patients undergoing to chemotherapy ABSTRACTBackground and Objective: Some neoplastic agents used in cancer treatment cause pulmonary toxicity and other important adverse effects, therefore, the present study aimed to evaluate the presence of obstructive lung disease (OLD), restrictive lung disease (RLD) or mixed in patients

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Revisiting bleomycin from pathophysiology to safe clinical use

Cited by 99 publications

References 74 publications

Role of endoplasmic reticulum stress in drug‐induced toxicity

Role of endoplasmic reticulum stress in drug‐induced toxicity

Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway

Avaliação da função pulmonar em pacientes com câncer submetidos à quimioterapia

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