Search results for " Damage"

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

Incomplete retention of radiation damage in zircon from Sri Lanka

2004

A suite of 18 zircon gemstones from placers in the Highland/Southwestern Complex, Sri Lanka, were subjected to a comprehensive study of their radiation damages and ages. The investigation included X-ray diffraction, Raman and PL spectroscopy, electron microprobe, PIXE and HRTEM analysis, as well as (U-Th)/He and SHRIMP U-Th-Pb age determinations. Zircon samples described in this study are virtually homogeneous. They cover the range from slightly metamict to nearly amorphous. Generally concordant U-Th-Pb ages averaging 555 ± 11 Ma were obtained. Late Ordovician zircon (U-Th)/He ages scattering around 443 ± 9 Ma correspond reasonably well with previously determined biotite Rb-Sr ages for rock…

OSSERVAZIONI SUI PUNITIVE DAMAGES IN PROSPETTIVA COMPARATISTICA

2016

Il tema dei 'punitive damages' offre lo spunto per una serie di considerazioni in ordine alle limitate possibilità di realizzazione, nell’ordinamento italiano, del trapianto giuridico di un istituto di common law, quale quello dei punitive damages nordamericani, sebbene in più occasioni, come già visto, si sia presentata l’occasione di una sua introduzione da parte della giurisprudenza italiana in sede di delibazione di sentenze straniere in materia. Nell'esaminare gli ostacoli alla realizzazione di tale trapianto giuridico, si sottolinea la forte resistenza all’introduzione di un rimedio risarcitorio con funzione punitiva per la sua incompatibilità con i principi di fondo del sistema itali…

SYNTHESIS OF PYRROLO[3,2-H]QUINOLINONES WITH GOOD PHOTOCHEMOTHERAPEUTIC ACTIVITY AND NO DNA DAMAGE

2010

In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.

Interstitial lung disease associated with drug therapy

2004

Drug-associated interstitial lung disease (ILD) is not uncommon, with diverse patterns ranging from benign infiltrates to the potentially fatal acute respiratory distress syndrome. As acute respiratory failure due to drug-associated ILD has an unpredictable onset and rapid time course, establishing a diagnosis is often difficult. An accurate diagnosis is based on clinical, radiological (including high-resolution computed tomography) and histological manifestations, although is often only possible by exclusion. Cancer chemotherapy is commonly associated with acute disease that, on pathology, is often diffuse alveolar damage. Furthermore, a combination of drugs with or without radiotherapy ca…

Heat shock protein Hsp70 expression and DNA damage in Baikalian sponges exposed to model pollutants and wastewater from Baikalsk Pulp and Paper Plant

2002

Abstract Lake Baikal, a unique habitat for a great number of endemic species, is the largest freshwater reservoir in the world which is still largely unaffected by anthropogenic pollution, except for some shore regions with industrial activity. The expressions of a biomarker of exposure (heat shock protein Hsp70) and a biomarker of effect (DNA single-strand breaks) were measured for the first time in endemic Baikalian sponge species (Baikalospongia intermedia, Lubomirskia fusifera, and Lubomirskia abietina). Tissue cubes of B. intermedia and dissociated cells of L. fusifera and L. abietina reacted to temperature stress (10–16 °C above ambient temperature) with a time-dependent increase in e…

The Role of DNA Damage in the Pathogenesis of Nitrate Tolerance

2013

SPARC oppositely regulates inflammation and fibrosis in bleomycin-induced lung damage.

2011

Fibrosis results from inflammatory tissue damage and impaired regeneration. In the context of bleomycin-induced pulmonary fibrosis, we demonstrated that the matricellular protein termed secreted protein acidic and rich in cysteine (SPARC) distinctly regulates inflammation and collagen deposition, depending on its cellular origin. Reciprocal Sparc(-/-) and wild-type (WT) bone marrow chimeras revealed that SPARC expression in host fibroblasts is required and sufficient to induce collagen fibrosis in a proper inflammatory environment. Accordingly, Sparc(-/-) >WT chimeras showed exacerbated inflammation and fibrosis due to the inability of Sparc(-/-) macrophages to down-regulate tumor necrosis …

Swelling, Acidosis, and Irreversible Damage of Glial Cells from Exposure to Arachidonic Acid in vitro

1994

Swelling and damage of C6 glioma cells and of primary cultured astrocytes were analyzed in vitro during incubation with arachidonic acid (AA; 20:4). The cells were suspended in a physiological medium supplemented with AA at concentrations of 0.001–1.0 m M. Cell swelling was quantified by flow cytometry with hydrodynamic focusing. Flow cytometry was also utilized for assessment of cell viability by exclusion of the fluorescent dye propidium iodide and for measurement of the intracellular pH (pHi) by 2′,7′-bis-(2-carboxyethyl)−5(and −6)carboxyfluorescein. Administration of AA caused an immediate dose-dependent swelling of C6 glioma cells, even at a concentration of 0.01 m M. At this level cel…

Radiolabeled DNase, a potential indicator for noninvasive detection of tissue damage

1983

Pancreatic DNase I was labeled with 131I or fluorescamine and injected IV into NMRI mice bearing a sarcoma 180. Of the injected tracer, 1.5%-2% was found to accumulate per g tumor. In sections of tumor tissue DNase was localized in damaged cells in solid and necrotic tumor regions. This binding is most probably due to specific interaction of DNase with actin, an ubiquitous cytoskeletal protein. Two-component blood clearance with a rapid first component (two-thirds of applied radioactivity) was observed. The labeled tumor could easily be visualized by gamma camera imaging. The findings suggest DNase to be a potent radiopharmaceutical for imaging damaged tissue, occurring in malignant tumors …