Inhaled chemotherapy in lung cancer: future concept of nanomedicine

Paul Zarogoulidis1, Ekaterini Chatzaki2, Konstantinos Porpodis1, Kalliopi Domvri1, Wolfgang Hohenforst-Schmidt3, Eugene P Goldberg4, Nikos Karamanos5, Konstantinos Zarogoulidis11Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Greece; 2Pharmacology Laboratory, Medical School, Democritus University of Thrace, Alexandroupolis, Greece; 3II Medical Clinic, Hospital Coburg, University of Wurzburg, Coburg, Germany; 4Biomaterials Science and Engineering, Department of Materials Science and Engineering, University of Florida, FL; 5Biochemistry Laboratory, Department of Chemistry, University of Patra, GreeceAbstract: Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.Keywords: inhaled chemotherapy, carriers, transducer

Pegylated liposomal doxorubicin in malignant pleural mesothelioma: a possible guardian for long-term survival

Paul Zarogoulidis,1,2 Maria Mavroudi,1 Konstantinos Porpodis,1 Kalliopi Domvri,1 Antonios Sakkas,3 Nikolaos Machairiotis,1 Aikaterini Stylianaki,1 Anastasios Tsiotsios,1 Nikolaos Courcoutsakis,4 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Pulmonary Department-Interventional Unit, Ruhrland Klinik, University of Essen, Essen, Germany; 3Department of Pathology, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4Department of Radiology, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: Malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura correlated with exposure to asbestos, with a medium survival of 11–12 months after diagnosis. A case of a 67-year-old male who had previously worked in the asbestos industry and is a current smoker is reported. The computed tomography evaluation revealed a right pleural mass with pleural thickening, and the pleural biopsy confirmed a diagnosis of malignant pleural mesothelioma. He was treated with chemotherapy consisting of etoposide, paclitaxel, and pegylated liposomal doxorubicin hydrochloride. After completion of chemotherapy, radiologic evaluation confirmed a reduction of pleural thickening and improvement in his symptoms. A complete presentation of each drug formulation and characteristics are also included in this paper. The patient’s follow-up is continuing, and computed tomography reveals stable disease 9 years after initial examination.Keywords: mesothelioma, asbestos, pegylated liposomal doxorubici

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer

Prospects of gene therapy for pulmonary diseases: Progress and limitations

Background: Despite the proof of principle that gene therapy can cure various monogenic diseases, limited clinical progress has been noted for gene therapy of the respiratory system. Certain anatomic features of the lungs, along with the suboptimal gene delivery vehicles utilized up to now, have significantly delayed successful clinical practice. Thus, the need for additional improvements towards safety and efficacy of the procedure is indispensable. Objective: The objective of this work was to review the progress and limitations of gene therapy in the treatment of lung disease with a focus on monogenic disease, chronic obstructive pulmonary disease and asthma and to present studies that provide a proof of principle that it works in different model systems and in patients. Method: A thorough search was performed on the aforementioned topic using Pubmed in order to identify relevant manuscripts. Several gene therapy studies for monogenic disorders affecting other organs or systems were also taken into consideration. Results: A hundred and thirty one papers were included. Inclusion criteria regarded novel gene transfer technologies of the past decade, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for pulmonary diseases. Conclusion: Current gene transfer protocols and vector design require additional amelioration. The rapidly evolving and much promising technology of CRISPR/Cas9 might possibly overcome the hurdles posed to date for effective implementation of gene therapy and become the basis for the onset of new clinical trials. © 2017 Bentham Science Publishers

Vitamin D in asthma and future perspectives

Haidong Huang,1 Konstantinos Porpodis,2 Paul Zarogoulidis,2,3 Kalliopi Domvri,2 Paschalina Giouleka,2 Antonis Papaiwannou,2 Stella Primikyri,2 Efi Mylonaki,2 Dionysis Spyratos,2 Wolfgang Hohenforst-Schmidt,4 Ioannis Kioumis,2 Konstantinos Zarogoulidis2 1Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People’s Republic of China; 2Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg–Essen, Essen, Germany; 4II Medical Clinic, “Coburg” Hospital, University of Würzburg, Coburg, Germany Abstract: Humans have the ability to synthesize vitamin D during the action of ultraviolet (UV) radiation upon the skin. Apart from the regulation of calcium and phosphate metabolism, another critical role for vitamin D in immunity and respiratory health has been revealed, since vitamin D receptors have also been found in other body cells. The term “vitamin D insufficiency” has been used to describe low levels of serum 25-hydroxyvitamin D that may be associated with a wide range of pulmonary diseases, including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. This review focuses on the controversial relationship between vitamin D and asthma. Also, it has been found that different gene polymorphisms of the vitamin D receptor have variable associations with asthma. Other studies investigated the vitamin D receptor signaling pathway in vitro or in experimental animal models and showed either a beneficial or a negative effect of vitamin D in asthma. Furthermore, a range of epidemiological studies has also suggested that vitamin D insufficiency is associated with low lung function. In the future, clinical trials in different asthmatic groups, such as infants, children of school age, and ethnic minorities are needed to establish the role of vitamin D supplementation to prevent and/or treat asthma. Keywords: vitamin D, asthma, immunomodulation, anti-inflammatio

Fat embolism due to bilateral femoral fracture: a case report

Konstantinos Porpodis1, Michael Karanikas2, Paul Zarogoulidis1, Maria Konoglou3, Kalliopi Domvri1, Alexandros Mitrakas2, Panagiotis Boglou4, Stamatia Bakali5, Alkis Iordanidis6, Vasilis Zervas1, Nikolaos Courcoutsakis6, Nikolaos Katsikogiannis7, Konstantinos Zarogoulidis11Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 21st Surgery Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 31st Pulmonary Department, “G Papanikolaou” General Hospital, Thessaloniki, Greece; 4Pulmonary Department, 5Microbiology Department, 6Radiology Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece; 7Surgery Department (NHS), University General Hospital of Alexandroupolis, Alexandroupolis, GreeceAbstract: Fat embolism syndrome is usually associated with surgery for large bone fractures. Symptoms usually occur within 36 hours of hospitalization after traumatic injury. We present a case with fat embolism syndrome due to femur fracture. Prompt supportive treatment of the patient’s respiratory system and additional pharmaceutical treatment provided the positive clinical outcome. There is no specific therapy for fat embolism syndrome; prevention, early diagnosis, and adequate symptomatic treatment are very important. Most of the studies in the last 20 years have shown that the incidence of fat embolism syndrome is reduced by early stabilization of the fractures and the risk is even further decreased with surgical correction rather than conservative management.Keywords: fat embolism syndrome, trauma, femur fracture, ARD

Roflumilast, a phosphodiesterase-4 inhibitor, induces phagocytic activity in Greek COPD patients

Konstantinos Porpodis,1 Kalliopi Domvri,1 Paul Zarogoulidis,1 Dimitrios Petridis,2 Katerina Tsirgogianni,1 Antonis Papaioannou,1 Olga Hatzizisi,3 Ioannis Kioumis,1 Alexandra Liaka,3 Violeta Kikidaki,3 Sofia Lampaki,1 John Organtzis,1 Konstantinos Zarogoulidis1 1Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, 2Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, 3Pulmonary Department, Immunology and Histocompatibility Laboratory, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Background: A new approach to the treatment of COPD includes controlling inflammation because of its important role in exacerbation of the disease. Recently, roflumilast has been added as a therapeutic option for COPD. Roflumilast is an oral phosphodiesterase-4 inhibitor that targets inflammatory cells involved in triggering exacerbations of COPD. The objective of the current study was to evaluate roflumilast for its contribution to phagocytic activity in COPD patients.Methods: Twenty-one patients diagnosed with COPD received roflumilast once daily for 6 months in combination with fluticasone (an inhaled corticosteroid), salmeterol (a long-acting β2-agonist), and tiotropium (a long-acting muscarinic antagonist) or combinations of these agents. The main inclusion criterion was stable disease for at least the previous 30 days. Neutrophils and spirometric changes, ie, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were measured in the COPD patients at indicated time points. The first sample was taken before receiving roflumilast, the second 3 months later, and the third after 6 months. Examination of defective phagocytosis was done by flow cytometry using a FagoFlowEx® kit. The statistical analysis was performed using Statistica software. Results: Our results indicate that phagocytic activity was increased after 3 and 6 months of treatment when compared with baseline (P<0.001). Similarly, FVC and FEV1 were also increased during the 6-month period, but only FVC differed significantly from baseline (P<0.001).Conclusion: Although the number of patients in this study was limited, our results indicate that roflumilast induces phagocytic activity, which improves lung function. Keywords: COPD, roflumilast, phosphodiesterase-4 inhibitor

Zarogouldis, P., et al., Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology. Int. J. Mol. Sci. 2012, 13, 10828-10862

The authors wish to add this correction on their paper published in IJMS [1]. The first author’s name is misspelled and the correct name is Paul Zarogoulidis. In addition, the 6th author’s name is incorrect and should be corrected to Wolfgang Hohenforst-Schmidt. These errors have been amended in an amended version of the manuscript, which is available from the International Journal of Molecular Sciences website. The authors and publisher apologize for the inconvenience. [...