Oxidative stress and inflammation contribute to lung toxicity after a common breast cancer chemotherapy regimen

2002 ◽  
Vol 283 (2) ◽  
pp. L336-L345 ◽  
Author(s):  
Amir M. Abushamaa ◽  
Thomas A. Sporn ◽  
Rodney J. Folz
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Chemotherapeutic Agents ◽  
Total Cell ◽  
Lung Toxicity ◽  
High Dose ◽  
Cell Counts ◽  
Cellular Inflammatory Response

Delayed pulmonary toxicity syndrome after high-dose chemotherapy (HDC) and autologous hematopoietic support occurs in up to 64% of women with advanced-stage breast cancer. Using a similar, but nonmyeloablative, HDC treatment regimen in mice, we found both immediate and persistent lung injury, coincident with marked decreases in lung tissue glutathione reductase activity and accompanied by increases in lung oxidized glutathione, bronchoalveolar lavage (BAL) lipid peroxidation, and BAL total cell counts. Most interestingly, at 6 wk, BAL total cell counts had increased fourfold, with lymphocyte cell counts increasing >11-fold. A single supplemental dose of glutathione prevented early lung injury at 48 h but showed no lung-protective effects at 6 wk, whereas single doses of other thiol-sparing agents (Ethyol and glutathione monoethyl ester) showed no benefit. These data suggest that this HDC regimen results in acute and persistent lung toxicity, induced in part by oxidative stress, that culminates with an acute lung cellular inflammatory response. Continuous glutathione supplementation and/or attenuation of the delayed pulmonary inflammatory response may prove beneficial in preventing lung toxicity after the use of these chemotherapeutic agents.

scholarly journals Redox Balance and Cellular Inflammation in the Diaphragm, Limb Muscles, and Lungs of Mechanically Ventilated Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 384-394 ◽  
Author(s):  
Judith Marín-Corral ◽  
Leticia Martínez-Caro ◽  
José A. Lorente ◽  
Marta de Paula ◽  
Lara Pijuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Protein Adducts ◽  
Organ Injury ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cellular Inflammation ◽  
Cell Counts ◽  
Limb Muscles

Background High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury. Methods Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]). Results The main findings are summarized as follows: compared with controls, (1) the diaphragms and gastrocnemius of high-VT rats exhibited a decrease in reactive carbonyls, (2) the soleus and tibialis of high- and moderate-VT rodents showed a reduction in reactive carbonyls and malondialdehyde-protein adducts, (3) the lungs of high-VT rats exhibited a significant rise in malondialdehyde-protein adducts, (4) the soleus and tibialis of both high- and moderate-VT rats showed a reduction in protein nitration, (5) the lungs of high- and moderate-VT rats showed a reduction in antioxidant enzyme levels, but not in the muscles, and (6) the diaphragms and gastrocnemius of all groups exhibited very low inflammatory cell counts, whereas the lungs of high-VT rats exhibited a significant increase in inflammatory infiltrates. Conclusions Although oxidative stress and inflammation increased in the lungs of rats exposed to high VT, the diaphragm and limb muscles exhibited a decline in oxidative stress markers and very low levels of cellular inflammation.

Leukemia risk following radiotherapy for breast cancer.

1989 ◽  
Vol 7 (1) ◽  
pp. 21-29 ◽  
Author(s):  
R E Curtis ◽  
J D Boice ◽  
M Stovall ◽  
J T Flannery ◽  
W C Moloney
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Radiation Dose ◽  
Cell Transformation ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Radiation Doses ◽  
Entire Body ◽  
Medical Physicists

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.

Acute interstitial pneumonitis following adjuvant tamoxifen therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11637-e11637 ◽  
Author(s):  
S. Ahmed ◽  
R. K. Shahid
Keyword(s):  
Breast Cancer ◽  
Lung Injury ◽  
Interstitial Pneumonitis ◽  
Ductal Carcinoma ◽  
Diffuse Alveolar Damage ◽  
Adjuvant Tamoxifen ◽  
Normal Lung ◽  
Excision Biopsy ◽  
High Dose ◽  
Menopausal Woman

e11637 Background: Tamoxifen is a serum estrogen receptor modulator that is widely used in the treatment of women with breast cancer and has a low incidence of serious side-effects. Although hypersensitivity reactions to tamoxifen have rarely been described, to our knowledge acute lung toxicity has not previously been reported. Objective: To report an unusual case of acute interstitial pneumonitis in a patient with early stage breast cancer treated with tamoxifen. Results: A 66 year old post-menopausal woman with past medical history of type 2 diabetes mellitus, and hypertension noted a lump in the right breast. An excision biopsy revealed 9 mm moderately differentiated invasive ductal carcinoma. Lymph nodes were not involvd by the tumor. The tumor cells were positive for estrogen and progesterone receptors and were negative for ErbB-2 over expression. The post operative course was complicated by wound infection treated with combination of clindamycin and ciprofloxacin. The patient was recommended adjuvant tamoxifen. Her other medication were metformin, valsartan, calcium and vitamin D. One week after the commencement of tamoxifen she noted increasing dyspnea, cough, and intermittent fever. X-ray chest showed bilateral lung infiltrates. She was hospitalized and treated with broad spectrum antibiotic. The patient condition deteriorated. She developed acute respiratory failure requiring intubation and mechanical ventilation. Tamoxifen was discontinued. A CT scan of chest showed bilateral interstitial infiltrates. Bronchoalveolar lavage was performed which was negative for infection. An open lung biopsy was done which showed focal diffuse alveolar damage consistent with interstitial pneumonia. No evidence of an infective agent, malignancy, or granuloma was noted. The patient was treated with high dose steroid. She gradually recovered and was discharge to home with normal lung function. Conclusions: Drug-induced lung injuries are usually idiosyncratic reactions and occur in an unpredictable manner. The presence of a temporal relationship between the lung injury and tamoxifen administration, a rapid clinical improvement after discontinuation of the drug, and absence of other causes strongly implicated tamoxifen as a potential cause of acute lung injury. No significant financial relationships to disclose.

scholarly journals Effect of penehyclidine hydrochloride on IL-6, TNF-α, HIF- 1α and oxidative stress in lung tissue of young rats with acute lung injury

2020 ◽  
Vol 19 (7) ◽  
pp. 1429-1433
Author(s):  
Jihong Shu ◽  
Zhenjiao Fang ◽  
Xinjun Xiong
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Tnf Α ◽  
Penehyclidine Hydrochloride ◽  
And Oxidative Stress

Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress

Assessment of combination approaches of phytoconstituents with chemotherapy for the treatment of breast cancer, a systematic review

2021 ◽  
Vol 27 ◽  
Author(s):  
Ali Sartaj ◽  
Sanjula Baboota ◽  
Javed Ali
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Treatment ◽  
Conventional Treatment ◽  
Breast Cancer Treatment ◽  
Chemotherapeutic Agents ◽  
Multi Drug Resistance ◽  
High Dose ◽  
Effective Strategy

Purpose: The available conventional treatment for breast cancer, like surgery, hormonal, radiation, and chemotherapy, given alone or in combination, is commonly used. Due to broad and diverse side effects, toxicity, and multi-drug resistance, chemotherapy has limited use and less effective treatment. In this review, anti-cancer drugs used in combination with phytoconstituents approaches have been summarised. It has been anticipated that this could be a promising and effective strategy for breast cancer treatment. Methods: This review is conducted based on relevant literature using the keywords presented in the title, abstract, and keywords. The available literature search in PubMed, ScienceDirect, MedlinePlus, and Google scholar up to May 2021. A total of 47 articles were selected out of 168 articles based on inclusion and exclusion criteria. Results: The significant drawbacks of available conventional treatment, especially chemotherapy, are low bioavailability for absorption at the specific site of tumor cells, development of multi-drug resistance, and high dose-related to various side effects. The phytoconstituents have anticancerous properties and chemotherapeutic agents that find a promising and potential therapeutics modality. Many in vitro and in vivo studies showed that phytoconstituents could enhance the effectiveness of chemotherapy drugs for breast cancer treatment. Conclusion: The combination approaches of phytoconstituents with chemotherapeutic drugs give less toxicity to normal cells, reduce side effects, and overcome the multi-drug resistance, making the combination approaches an effective strategy.

scholarly journals Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways

QJM ◽  
2019 ◽  
Vol 112 (12) ◽  
pp. 914-924 ◽  
Author(s):  
Y Fang ◽  
F Gao ◽  
Z Liu
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Hyperoxic Lung Injury ◽  
Expression Activity ◽  
And Oxidative Stress

Summary Objective To investigate the role of angiotensin-converting enzyme 2 (ACE2) in hyperoxic lung injury. Methods Adult mice were exposed to 95% O2 for 72 h to induce hyperoxic lung injury, and simultaneously treated with ACE2 agonist diminazene aceturate (DIZE) or inhibitor MLN-4760. ACE2 expression/activity in lung tissue and angiotensin (Ang)-(1–7)/Ang II in bronchoalveolar lavage fluid (BALF), and the severity of hyperoxic lung injury were evaluated. The levels of inflammatory factors in BALF and lung tissue and the expression levels of phospho-p65, p65 and IkBα were measured. Oxidative parameter and antioxidant enzyme levels in lung tissue were measured to assess oxidative stress. Finally, the expression levels of nuclear factor-erythroid-2-related factor (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were measured using Western blotting. Results Hyperoxia treatment significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1–7) ratio, while co-treatment with hyperoxia and DIZE significantly increased lung ACE2 expression/activity and decreased the Ang II/Ang-(1–7) ratio. By contrast, co-treatment with hyperoxia and MLN-4760 significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1–7) ratio. Hyperoxia treatment induced significant lung injury, inflammatory response and oxidative stress, which were attenuated by DIZE but aggravated by MLN-4760. The NF-κB pathways were activated by hyperoxia and MLN-4760 but inhibited by DIZE. The Nrf2 pathway and its downstream proteins NQO1 and HO-1 were activated by DIZE but inhibited by MLN-4760. Conclusion Activation of ACE2 can reduce the severity of hyperoxic lung injury by inhibiting inflammatory response and oxidative stress. ACE2 can inhibit the NF-κB pathway and activate the Nrf2/HO-1/NQO1 pathway, which may be involved in the underlying mechanism.

scholarly journals Salivary proline rich peptide decreases cell growth in HCC38 triple negative breast cancer cell line

2017 ◽  
Vol 7 (2) ◽  
pp. 38 ◽  
Author(s):  
Charles F. Streckfus ◽  
Daniel Arreola ◽  
Cynthia G. Streckfus ◽  
Lenora R. Bigler
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Normal Tissue ◽  
Triple Negative ◽  
Cancer Cell Line ◽  
High Dose ◽  
Cell Counts ◽  
Proline Rich Peptide

Objective: The objective of this study is to determine the effects of p1978 on the growth rate of a triple receptor negative breast cancer cell line.Methods: Three cell lines, 185B5 normal tissue, HCC38, and AU585, were seeded with peptide p1978. Corresponding plates were seeded with PBS to serve as controls. Baseline line cell counts were taken at 30% confluence prior to seeding. Counts were again made 48 hours later.Results: The HCC38 cell line showed decreased growth when exposed to the low and high dose of p1978 peptide.Conclusion: The results suggest that p1978 may have potential in treating triple receptor negative breast cancer.

scholarly journals Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B

2008 ◽  
Vol 26 (14) ◽  
pp. 2364-2372 ◽  
Author(s):  
Michael P. DiGiovanna ◽  
David F. Stern ◽  
Susan Edgerton ◽  
Gloria Broadwater ◽  
Lynn G. Dressler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Breast Cancer Study ◽  
Dosing Regimens ◽  
Her 2 ◽  
Group B ◽  
The Impact ◽  
Leukemia Group

PurposeErbB-2 (human epidermal growth factor receptor 2) overexpression may be predictive of relative resistance and/or sensitivity to specific chemotherapeutic agents. Results from a previous study from the Cancer and Leukemia Group B (CALGB 8541) demonstrated an interaction between ErbB-2 and increasing dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) chemotherapy. Other studies have suggested that evaluation of the phosphorylated/activated form of ErbB-2 might be more precise in defining the impact of ErbB-2 in breast cancer. We have evaluated tumor tissue sections from CALGB 8541 patients to determine whether the interaction of ErbB-2 with CAF dose is dependent on ErbB-2 activation state, and whether phosphorylated ErbB-2 is an adverse prognostic factor in patients treated with CAF.Patients and MethodsPatients were randomly assigned to one of three dosing regimens of CAF. Paraffin samples from 992 of 1,572 patients who participated in CALGB 8541 were available. Of the 570 tumors with any staining for ErbB-2, 488 had tissue available for assay for phosphorylated ErbB-2, which was performed by immunohistochemistry.ResultsOf 910 total assessable cases, 112 of 488 ErbB-2-positive cases (23%) stained positively for phosphorylated ErbB-2. The previously described interaction of dosing regimen of CAF with ErbB-2 was not dependent on phosphorylation status of ErbB-2.ConclusionMonitoring phosphorylation of ErbB-2 with an antiphospho-ErbB-2 antibody did not add further precision to identifying those patients most likely to benefit from increased dose of anthracycline-based adjuvant chemotherapy. Favorable outcomes are observed in ErbB-2-overexpressing patients treated with high-dose CAF regardless of ErbB-2 phosphorylation state.

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