Pleural Mesothelioma Definations
source (google.com)The purpose of this study was to investigate the antiproliferative potential of two novel bio-organometallic drug candidates, based on hydroxyl-phenyl-but-1-ene skeleton and containing the ferrocenyl (Fc) moiety, namely ferrociphenol (Fc-diOH) and ferrocifen (Fc-OH-TAM), on two cell lines, named BR95 (epithelial-like) and MM98 (sarcomatous-like), obtained from pleural effusions of previously untreated malignant pleural mesothelioma (MPM) patients. In vitro chemosensitivity of MPM cells towards the title compounds was evaluated by cell viability assay, alkaline Single Cell Gel Electrophoresis (Comet test) and western blotting evaluation of p53 induction. The two bio-organometallic derivatives were found to be more potent in inhibiting cell proliferation than the reference metallo-drug cisplatin (CDDP). This antiproliferative effect cannot be attributed to estrogenic/antiestrogenic activity, since both cell lines resulted to be estrogen insensitive (ER−). Fc-diOH and CDDP were able to upregulate wild type p53 present in MM98 cell line, while Fc-OH-TAM was not. Similarly, Fc-diOH and CDDP induced early DNA damage, while Fc-OH-TAM did not. This indicates that, albeit the similar structures, the two ferrocifens exhert different mechanisms of cytotoxicity on MPM cells.
Proposed intracellular activation of Fc-diOH giving rise to alkylating quinine methide. This complex pathway corresponds to intracellular oxidation of ferrocenyl moiety, followed by removal of a phenolic proton, leading to the formation of a quinone methide, an electrophilic species able to react with macromolecules, especially DNA leading to genotoxic effects.cisplatin or CDDP, cis-diamminedichloroplatinum (II); Comet assay, single cell gel electrophoresis; CT, continuous treatment; E2, estrogen; ER−, estrogen insensitive; ER, estrogen receptor; ER+, estrogen sensitive; Fc-diOH, (1,1-bis(4-hydroxy-phenyl)-2-ferrocenyl-but-1-ene: ferrociphenol; Fc-OH-TAM, 1-[4-(-O(CH2)3NMe2)phenyl]-1-(4-hydroxy-phenyl)-2-ferrocenyl-but-1-ene): ferrocifen; HRP, horse radish peroxidase; MM, malignant mesothelioma; MPM, malignant pleural mesothelioma; MTS, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium); PBS, phosphate buffered saline; R, recovery; TAM, tamoxifenFig. 3. Cell viability of BR95 (left column) and MM98 (right column) following CDDP, Fc-diOH or Fc-OH-TAM at 24 h CT (24 CT), 24 h CT followed by 48 h of R (24 h CT + 48 h R), or 72 h CT (72 h). Results are means of 3–8 replications of the same experiment, p < 0.05.Fig. 4. Comet assay: (a) BR95 comet head diameter, (b) BR95 comet tail length, (c) MM98 comet head diameter, and (d) MM98 comet tail length. Data are expressed in pixels (px). Untreated cells (NT) were used as controls for the unpaired
V.B. Antony
V.B. Antony, Indiana University School of Medicine, Pulmonary and Critical Care Medicine, RL Roudebush VA Medical Center, 1481 West 10th Street, Indianapolis, IN, 46202. Tel: 317/554-0036, USA. Fax: 317 5540262. E‐mail: vantony@iupui.eduThe pleural membrane consisting of pleural mesothelial cells and its underlying connective tissue layers play a critical role in immunological responses in both local and systemic diseases. The pleura, because of its intimate proximity to the lung, is positioned to respond to inflammatory changes in the lung parenchyma. Importantly, several systemic diseases have a predilection for expression on the pleural surface.
Immunological responses in the pleura include the development of pleural permeability and pleural effusion formation as well as the development of pleural fibrosis and scarring. Under either circumstance, the normal functioning of the pleura is impaired and has multiple consequences leading to increased morbidity and even mortality for the patient.
During infections in the pleural space, the pleural mesothelium responds by actively recruiting inflammatory phagocytic cells and allowing the movement of proteins from the vascular compartment into the pleural space. The release of chemokines by the pleural mesothelium allows for directed migration of phagocytic cells from the basilar surface of the pleura towards the apical surface.
In malignant disease, the pleura may be the site of primary tumours such as mesothelioma and also the site for malignant metastatic deposits. Certain cancers such as cancers of the breast, ovary, lung, and stomach have a predilection for the pleural mesothelium. The process whereby malignant cells attach to the pleural mesothelium and develop autocrine mechanisms for survival in the pleural space are elucidated in this review. The pleura functions not only as a mechanical barrier, but also as an immunologically and metabolically responsive membrane that is involved in maintaining a dynamic homeostasis in the pleural space.
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
Pleural Mesothelioma Lung X ray Histology CXR CT Cancer Ribbon Cytology Symptoms Commercial
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