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Retinoid-related molecules (RRM) are novel agents with tumor-selective cytotoxic/antiproliferative activity, a different mechanism of action from classic retinoids and no cross-resistance with other chemotherapeutics. ST1926 and CD437 are prototypic RRMs, with the former currently undergoing phase I clinical trials. We show here that ST1926, CD437, and active congeners cause DNA damage. Cellular a
PURPOSE: After DNA damage, checkpoints pathways are activated in the cells to halt the cell cycle, thus ensuring repair or inducing cell death. To better investigate the role of checkpoint kinase 1 (Chk1) in cellular response to different anticancer agents, Chk1 was knocked down in HCT-116 cell line and in its p53-deficient subline by using small interfering RNAs (siRNA).EXPERIMENTAL DESIGN: Chk1
Trabectedin (ET-743, Yondelis) is a natural marine compound with antitumour activity currently undergoing phase II/III clinical trials. The mechanism of the drug's action is still to be defined, even though it has been clearly demonstrated the key role of Nucleotide Excision Repair (NER). To get further insights into the drug's mode of action, we studied the involvement of the DNA-double strand br
TO-PRO-3 iodide (TP3), a monomeric cyanine nucleic acid stain with a peak absorbance at 642 nm and emission at 661 nm, is best excited by a helium-neon (HeNe) laser (633nm). It was tested in monocytes and different cell lines under conditions of different fixatives, dye concentrations, labeling kinetics and RNAse concentrations for mono-, bi- and tri-parametric flow cytometric cell cycle analysis
OBJECTIVES: Trabectedin (ET-743, Yondelis) is a natural marine product, with antitumour activity, currently in phase II/III clinical trials. Previous studies have shown that cells hypersensitive to ultraviolet (UV)-rays because of nucleotide excision repair (NER) deficiency, were resistant to trabectedin. The purpose of this study was to investigate whether this resistance was associated with diff
Drug design based on the structure of specific enzymes playing a role in carcinogenesis, e.g. tyrosine kinases, has been successful at identifying novel effective anticancer drugs. In contrast, no success has been achieved in drug design attempts, in which transcription factors or DNA-transcription factor complexes involved in the pathogenesis of human neoplasms were targeted. This failure is like
The retinoid-related molecules (RRMs) ST1926 [(E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid] and CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid) are promising anticancer agents. We compared the retinoic acid receptor (RAR) trans-activating properties of the two RRMs and all-trans-retinoic acid (ATRA). ST1926 and CD437 are better RARgamma agonists than ATRA. We
This paper illustrates some biochemical and pharmacological properties of two natural marine products such as trabectedin (ET-743, Yondelis) and aplidine. Trabectedin has shown clinical antitumor activity in refractory soft tissue sarcoma and ovarian cancer. The lack of cross resistance of trabectedin with other chemotherapeutic drugs is presumably related to its peculiar mode of action, that seem
In the near future, the number of connected mobile devices and data-rates are expected to dramatically increase. Demands exceed the capability of the currently deployed (4G) wireless communication systems. Development of 5G systems is aiming for higher data-rates, better coverage, backward compatibility, and conforming with “green communication” to lower energy consumption. Massive Multiple-Input
Remains of a basilican round church were discovered in 1877–78 in Tønsberg, Norway, and identified as the Premonstratensian monastery church of Saint Olav. The round church has been interpreted as fortified with several floors using Nylars on Bornholm in Denmark as a model – or as symbolic copy of Holy Sepulchre in Jerusalem, although Templar churches have also been mentioned as models. The church
In the presented paper experimental and numerical analyses are made of the failure due to blister formation in moist packaging material when exposed to excessive heating. The basic concept of the experimental analysis is to expose a package material to a hot air jet and measure the time until the material experience internal failure. For the numerical analysis, a triphasic macroscale hybrid mixtur
A growing set of policies involve transfers conditioned upon socially desired actions, such as attending school or conserving forest. However, given a desire to maximize the impact of limited funds by avoiding transfers that do not change behavior, typically some potential recipients are excluded on the basis of their characteristics, their actions or at random. This paper uses a laboratory experi
Råttan är en däggdjursart med en kort dräktighetstiden och föds därför mycket omogen. Den är vid födelsen naken, blind och döv och är helt beroende av sin moder för många funktioner, såsom näringstillförsel, termoreglering, urinering och tarmtömning. Under diperioden är råttans mag-tarmsystem och matsmältning helt anpassad till modersmjölkdieten. Bland annat är tarmens barriärfunktion omogen, vilkThe rat, as an altritial species, is born with an immature gastrointestinal tract and intestinal barrier function, which is highly absorptive to milk-borne bioactive molecules that can pass undigested and reach the general circulation of the suckling newborn. This passage occurs by the neonatal-Fc-receptor (FcRn) binding and trancytosis of immunoglobulin G in the proximal small intestine (SI) and
Populärhistorisk översikt över relationerna mellan Lunds universitet och svenska monarker (och en kronprins) vid namn Carl från Carl X Gustaf till Carl XVI Gustaf.
BACKGROUND: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. METHODS: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical
Varje cell har ett membran som skapar en gräns mot omvärlden och skyddarcellen. Men cellen måste alltjämt utbyta viktiga molekyler med omvärlden för attöverleva. Därför finns specialiserade proteiner, som sitter i membranen och utgörportar i denna barriär. Denna avhandling fokuserar på två membranproteiner, enprotonpump och en jonkanal.Varje dag i våra liv använder vi hjärnan, muskler och hjärtat.NADH:quinone oxidoreductase (Complex I) is the first enzyme of the respiratory chain and is involved in energy conservation generating an electro-chemical gradient across a membrane. The enzyme can be divided into a membrane spanning domain and a hydrophilic domain, which protrudes from the membrane. In the hydrophilic domain electrons from NADH oxidation are transported via a wire of iron-sulfur
Over the past decade, the advances in grating-based soft X-ray spectrometers have revolutionizedthe soft X-ray spectroscopies in materials research. However, these novel spectrometers are mostlydedicated designs, which cannot be easily adopted for applications with diverging demands. Here wepresent a versatile spectrometer design concept based on the Hettrick-Underwood optical scheme thatuses modu
Det finns i Sverige en allt tydligare politisk vilja att katalysera digitalisering- en av offentlig sektor, inklusive det kommunala sociala arbetet. Samtidigt pågår också en omfattande digitalisering av det svenska samhället överlag som det kommunala sociala arbetet har att hantera både på organisations-, handläggar- såväl som brukarnivå. Men hur ser det forskningsbaserade kunskapsläget ut?Vi redo
