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      Drug-induced Interstitial Lung Disease in Breast Cancer Patients: A Lesson We Should Learn From Multi-Disciplinary Integration


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          Taxanes represented by paclitaxel and targeted therapy including trastuzumab are two common agents for human epidermal growth factor receptor-2 (HER-2)-positive breast cancer patients. Effectiveness, however, usually comes at the cost of many side effects, some of which are even fatal. Drug-induced interstitial lung diseases (DILDs) comprise a group of drug-induced pulmonary injuries usually caused by using these medications. For DILDs, systemic therapy can be harmful to lung tissues and rapidly threaten the lives of some breast cancer patients. Through the cases from our hospital and related studies in medical databases, we hope readers can learn a lesson from an angle of multi-disciplinary integration based on clinical practice and pharmacological mechanisms to make anti-cancer agents less harmful and reduce the incidence of DILD in breast cancer patients during systemic therapy.

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          Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies.

          Infection is one of the leading causes of morbidity and mortality in systemic lupus erythematosus (SLE). Bacterial infections are most frequent, followed by viral and fungal infections. The impaired cellular and humoral immune functions seen in patients with SLE are predisposing conditions, whilst disease activity, prednisone doses over 7.5-10 mg/day, high doses of methylprednisolone or cyclophosphamide are well-recognised risk factors for infection. The first six months after rituximab treatment and the use of more than three courses are also associated with an increased susceptibility for infection. It has not been established whether belimumab, azathioprine and mycophenolate mofetil increase the risk of serious infections. Most vaccines are effective and safe in SLE patients, although vaccination should be avoided during periods of active disease. Live virus vaccines are contraindicated for immunosuppressed patients. Influenza and pneumococcal vaccines are universally recommended. Tuberculosis prophylaxis should be considered in selected cases. Therefore, it is advisable not to exceed doses of 5 mg/day of prednisone in chronic treatment. Methylprednisolone and cyclophosphamide should be used in low-dose regimens. Antimalarials have a well-known protective role against infection, in addition to other beneficial properties, thus, hydroxychloroquine is recommended for all SLE patients where no contraindication exists.
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            Novel action of paclitaxel against cancer cells: bystander effect mediated by reactive oxygen species.

            Generation of reactive oxygen species (ROS) has been observed in cancer cells treated with paclitaxel, but the underlying mechanisms and therapeutic implications remain unclear. In the present study, we showed that paclitaxel promoted ROS generation through enhancing the activity of NADPH oxidase (NOX) associated with plasma membranes. Treatment of breast cancer cells caused an increased translocation of Rac1, a positive regulatory protein of NOX, to the membrane fraction. The paclitaxel-induced ROS generation occurred rapidly within several hours of drug exposure, with O(2)(-) and H(2)O(2) accumulation mainly outside the cells while the intracellular ROS remained unchanged. Importantly, the increase in extracellular ROS caused lethal damage to the bystander cancer cells not exposed to paclitaxel, as shown by two different methods using coculture systems where the bystander cells were differentiated from the paclitaxel-treated cells by fluorescent or radioactive labeling. This cytotoxic bystander effect was also observed with other microtubule-targeted agents vincristine and taxotere but not with 5-fluorouracil or doxorubicin. This toxic bystander effect was enhanced by CuZnSOD that converts O(2)(-) to H(2)O(2) and was abolished by a catalase that eliminates H(2)O(2). Furthermore, paclitaxel was able to induce an almost complete inhibition of proliferation of the bystander cells in the coculture system. Our study revealed a novel mechanism by which paclitaxel induces toxic bystander effect through generation of extracellular H(2)O(2) from the membrane-associated NOX. This may contribute to the potent anticancer activity of paclitaxel and provide a novel basis to improve the clinical use of this important drug.
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              Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial.

              Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

                Author and article information

                BIO Integration
                Compuscript (Ireland )
                01 September 2020
                20 July 2020
                : 1
                : 2
                : 82-91
                [1] 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, P.R. China
                [2] 2Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P.R. China
                [3] 3Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P.R. China
                Author notes
                Corresponding author: Yan Nie, Department of Breast Tumor Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, P.R. China, E-mail: nieyan7@ 123456mail.sysu.edu.cn
                Copyright © 2020 Bio Integration

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See https://bio-integration.org/copyright-and-permissions/

                : 18 April 2020
                : 12 May 2020
                : 29 May 2020
                Self URI (journal-page): https://bio-integration.org/
                Case Report

                Medicine,Molecular medicine,Radiology & Imaging,Biotechnology,Pharmacology & Pharmaceutical medicine,Microscopy & Imaging
                taxanes,multi-disciplinary integration,trastuzumab,drug-induced interstitial lung disease,Breast cancer


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