27 research outputs found
Critical Role of Aquaporins in Cancer: Focus on Hematological Malignancies
No full textAquaporins are transmembrane molecules regulating the transfer of water and other compounds such as ions, glycerol, urea, and hydrogen peroxide. Their alteration has been reported in several conditions such as cancer. Tumor progression might be enhanced by aquaporins in modifying tumor angiogenesis, cell volume adaptation, proteases activity, cell–matrix adhesions, actin cytoskeleton, epithelial–mesenchymal transitions, and acting on several signaling pathways facilitating cancer progression. Close connections have also been identified between the aquaporins and hematological malignancies. However, it is difficult to identify a unique action exerted by aquaporins in different hemopathies, and each aquaporin has specific effects that vary according to the class of aquaporin examined and to the different neoplastic cells. However, the expression of aquaporins is altered in cell cultures and in patients with acute and chronic myeloid leukemia, in lymphoproliferative diseases and in multiple myeloma, and the different expression of aquaporins seems to be able to influence the efficacy of treatment and could have a prognostic significance, as greater expression of aquaporins is correlated to improved overall survival in leukemia patients. Finally, we assessed the possibility that modifying the aquaporin expression using aquaporin-targeting regulators, specific monoclonal antibodies, and even aquaporin gene transfer could represent an effective therapy of hematological malignancies
Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker
No full textColorectal cancer (CRC) is one of the most common tumors in developed countries. The five-year survival rate decreases depending on how advanced the CRC is when first diagnosed. Screening has been proven to greatly reduce mortality from colorectal cancer, but an ideal screening tool is far from being established. Here, we aimed to discover and validate early CRC biomarkers by means of an untargeted/targeted metabolomic approach. A preliminary untargeted analysis of plasma lipids performed on a small patient cohort (30 plasma samples) revealed some alterations that occurred in the presence of this tumor. In particular, medium-chain fatty acids with between six and twelve carbon atoms (C6-C12) were found to be the lipid class that showed the most marked changes upon the development of CRC. In order to evaluate the utility of this lipid class as diagnostic CRC biomarkers, a further study based on a wider cohort of patients (117 plasma samples) was performed. Using a targeted approach, these fatty acids were quantified in plasma samples by means of fast gas chromatography coupled to a time-of-flight analyzer. Plasma samples from patients with CRCs at different tumor stages were analyzed and compared to those from healthy subjects, ulcerative colitis patients, high-grade dysplasia adenoma patients, and breast cancer patients in order to test the specificity and sensitivity of these possible biomarkers. Results revealed significant differences among the considered groups in terms of their C6, C8, C10, and C12 fatty acid plasma concentrations. In particular, receiver operating characteristic (ROC) curves obtained for the C10 fatty acid gave an area under the curve of 0.8195 along with a sensitivity of 87.8 % and a specificity of 80 %, strongly suggesting that it could be a valuable early diagnostic biomarker of CRC
Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle
No full textIn this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules
Safeguarding Bee Health: Insights from a Collaborative Monitoring and Prevention Project Against Pesticide Poisonings
No full textIn recent decades, bee poisoning due to pesticides and agrochemicals has increased, posing significant challenges to honey bee health and contributing to the so-called “Colony Collapse Disorder” (CCD). Poor knowledge about the level of exposure of bee colonies to pesticides and agrochemicals, whether from the environment or beekeeping management practices, is a major limiting factor in preventing these diseases. Collaboration among different stakeholders, such as beekeeping associations, local veterinary authorities, and researchers, is essential to create monitoring programs that can collect these data and enable the prompt implementation of surveillance and preventive actions to address potential bee colony poisoning incidents caused by these contaminants. The present study describes the results obtained through a collaborative initiative that was implemented for monitoring and preventing pesticide-induced bee poisonings in a territory of northern Italy where the exposure of honey bee colonies to different types of pesticides and agrochemicals may occur. Four sentinel apiaries were selected based on possible sources of pollution throughout the territory. Pollen samples were collected at different times during the years 2021–2022 and analyzed for pesticides using gas and liquid chromatography tandem quadrupole mass spectrometry (GC-MS/MS and LC-MS/MS) techniques. The findings showed the presence of a number of pesticides, such as pyrethroids, permethrin, cypermethrin, amitraz, and pendimethalin, at varying concentrations. Acute bee mortality was observed in a field case related to pyrethroid exposure in 2022, in an urban area. These results confirm the need for timely interventions, improved sampling methods, and continuous monitoring to safeguard bee populations. Collaboration with local beekeepers and public authorities is thus essential in addressing pesticide use and bee health challenges, fostering efficient communication and training efforts to support sustainable beekeeping
Extracellular Vesicles Shed by Melanoma Cells Contain a Modified Form of H1.0 Linker Histone and H1.0 mRNA-binding Proteins
No full textExtracellular vesicles (EVs) are shed in the extracellular environment by both prokaryotes and eukaryotes. Although produced from both normal and cancer cells, malignant cells release a much higher amount of EVs, which also contain tumor-specific proteins and RNAs.
We previously found that G26/24 oligodendroglioma cells shed EVs that contain the pro-apoptotic factors FasL and TRAIL1-2. Interestingly, G26/24 release, via EVs, extracellular matrix remodelling proteases3, and H1° histone protein4, and mRNA. To shed further light on the role of EVs in discarding proteins and mRNAs otherwise able to counteract proliferative signals, we studied a melanoma cell line (A375). We found that also these cancer cells produce H1° and release it into the extracellular space by EVs. Interestingly, H1° sorted to vesicles has a molecular mass higher than expected, and is probably sumoylated. By T1 RNase-protection assay with the H1° RNA, three main complexes were evidenced in EVs, the most abundant of which has a molecular mass of about 65 kDa. By using a biotinylated H1° RNA to fish interacting factors, we isolated from EVs a few proteins which have been then identified by mass spectrometry: the most abundant is a protein of about 60 kDa: myelin expression factor-2 (MYEF2). Western blot analyses confirmed the presence of MYEF2 in EVs released from A375 melanoma cells.
1. D’Agostino et al. 2006, Int J Oncol 29:1075-85.
2. Lo Cicero A et al. 2011, Int J Oncol 39:1353-57.
3. Lo Cicero A et al. 2012, Matrix Biol 31: 229-33.
4. Schiera G et al. 2013, Int J Oncol 43: 1771-76
Synthesis and antiproliferative activity of 3-(2-cloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one
No full textBased on the encouraging results found for 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one 7 previously tested by us, as well as the consideration that heterocycle fused tetrazepinones bearing the 2-chloroethyl substituent show a better cytotoxic profile than temozolomide and mitozolomide against human cancer cell lines which express the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), in this paper we report the multistep synthesis and the biological study of 3-(2-cloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one 10. Like compound 7, it was active on P-glycoprotein expressing cells (MDR) HL60 and on K562 cell line that are resistant to apoptosis induced by different stimuli, showing GI50 values of 14 and 18 μM respectively. As an antiproliferative agent against the above cells compound 10 was about 2.2 times more active than compound 7. Compound 10 was also tested against WiDR cells which are overexpressing the DNA repair protein MGMT, showing a GI50 value of 2.3 μM. Finally, concerning the effect on cell cycle we observed an evident difference between compounds 7 and 10. In fact, compound 7 induces a block of cell cycle in G0-G1, therefore acting as phase-specific drug, in contrast, compound 10 is a not phase-specific agent. Both the compounds are able to increase the apoptotic sub G0-G1 peak of cell cycle
Synthesis and antioproliferative activity of new derivatives containing the policyclic sistem 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3'.4':2,3]azepino[4,5-f]azocine
No full textBy reacting methylaminopyrazoles with hexane-2,5-dione in 1,4-dioxane in the presence of p-toluensulfonic acid, new derivatives containing the policyclic sistem 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3'.4':2,3]azepino[4,5-f]azocine were obtained. The new synthesized compounds were tested preliminarly at 10 microM against five human cancer cell lines showing a range of inhibition of 20-62% against the most susceptible cell lines K562 and HCT116
Synthesis and anti-staphylococcal activity of new 4-diazopyrazole derivatives
No full textSeveral new 4-diazopyrazole derivatives 6a-g and 9a-c were obtained by the reaction of 1-(R-substituted phenyl)-3-(1,3-dimethyl-1H-pyrazol-5-yl)ureas 5a-g and N-(1,3-dimethyl-1H-pyrazol-5-yl)-2-(R-substituted phenyl)acetamides 8a-c respectively with a sevenfold excess of nitrous acid in acetic acid solution. The compounds were assayed for their activity against the Staphylococcus aureus reference strains ATCC 25923, ATCC 29213 and ATCC 6538, as well as six veterinary strains. The best anti-staphylococcal profile was showed by [(R-substituted phenyl)acetyl](4-diazonio-1,3-dimethyl-1H-pyrazol-5-yl)azanides 9a,c. The compound 9c was also able at 3.1 μg mL-1 to inhibit of 45.7% the biofilm formation of the strains S.aureus ATCC 29213
Isoxazolo[3,4-d]pyridazin-7(6H)-one derivatives endowed with anti-proliferative Activity.
No full textIsoxazolo[3,4-d]pyridazin-7(6H)-one derivatives endowed with antiproliferative Activity
B. Maggio1, G. Cancemi1, D. Raffa1, M. V. Raimondi1, F. Plescia1, A. D’Anneo2,M. Lauricella3, G. Barone4, R. Bonsignore4, G. Daidone1
1. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Medicinal Chemistry and
Pharmaceutical Technologies Section, University of Palermo, ViaArchirafi 32, 90123, Palermo, Italy
2. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry,
University of Palermo.
3.Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of
Palermo.
4. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo.
[email protected]
A screening carried out by NCI (Bethesda, USA) on compounds available in our laboratory,in order to
ascertain their antiproliferative activity against a panel of 60 human tumor cell lines, allowed to discovery
the 3,4-diphenylisoxazolo[3,4-d]pyridazin-7(6H)-one 1a [1] as an hit compound, often showing GI50values
at sub-micromolar level. We synthesized some analogs of 1a, i.e.1b-gand other derivatives in which the
NHgroup is variably alkylated, with the aim to obtain more active compounds as well as to perform
structure-activity relationship(SAR) studies.
We obtained a quite active antiproliferative compound, the 3,4-di-p-tolylisoxazolo[3,4-d]pyridazin-7(6H)-
one 1d, and verified the importance for the antiproliferative activity of the aril, and not alkyl, groups linked
to the isoxazolo-pyridazinone moiety. Studies performed on the cell cycle progression and on some cellular
target (ATM, procaspase-2 proteins and H2AX histone) demonstrated that 1d produces an increase of the
cell population in pre-G0/G1 and induces cellular death by apoptosis, damaging the DNA by double strand
breaks. UV-vis titration and viscosity measurement showed that the compound is able to give an interaction
with the B-DNA.
1. Renzi G., Dal Piaz V. (2004)Gazz. Chim. It.95: 1478–149
