19 research outputs found
Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives
Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity against cancer cells in comparison with 5-fluorouracile. Among all tested compounds, some compounds substituted with cyano groups showed a pronounced and selective activity in the nanomolar range of inhibitory concentrations against HeLa and HepG2. The strongest selective activity against HeLa cells was observed for acrylonitriles 8 and 11 and their cyclic analogues 15 and 17 substituted with two cyano groups with a corresponding IC50 = 0.33, 0.21, 0.65 and 0.45 μM, respectively. Compounds 11 showed the most pronounced selectivity being almost non cytotoxic to normal fibroblasts. Additionally, mode of biological action analysis was performed in silico and in vitro by Western blot analysis of HIF-1-α relative expression for compounds 8 and 11
Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4 regulatory sequences
Respiratory Syncytial Virus Matrix Protein Induces Lung Epithelial Cell Cycle Arrest through a p53 Dependent Pathway
Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication
Functional SNP in microRNA‐491‐5p binding site of MMP9 3′‐UTR affects cancer susceptibility
Sixty years of global progress in managed aquifer recharge
Sessanta anni di progressi a livello globale nella ricarica delle falde acquifere in condizioni controllate
Riassunto
Gli ultimi 60 anni sono stati testimoni di prelievi e fenomeni di sovrasfruttamento delle falde senza precedenti, come pure dello sviluppo di nuove tecnologie per il trattamento delle acque. Questi fattori hanno guidato i progressi nelle applicazioni della ricarica intenzionale degli acquiferi, nota in lingua inglese come managed aquifer recharge – MAR (in italiano tradotto in “ricarica delle falde in condizioni controllate”). Questo articolo è il primo tentativo conosciuto dagli Autori che ha l’obiettivo di quantificare a scala globale il volume prodotto attraverso tecniche MAR, di illustrare i progressi compiuti nelle varie tipologie di MAR e di mettere questi in relazione con gli avanzamenti nella ricerca e nella regolamentazione. Di fronte al cambiamento del clima e all’aumento dell’intensità degli eventi climatici estremi, le tecniche MAR rappresentano una strategia di gestione delle acque sempre più importante, insieme alla gestione della domanda, per mantenere, migliorare e proteggere i sistemi acquiferi sotto pressione e per salvaguardare e migliorare la qualità delle acque. In questo arco di tempo, la ricerca scientifica relativa alla progettazione idraulica degli impianti, agli studi con traccianti, alla gestione dei fenomeni di intasamento, all’efficienza di recupero ed. alle modifiche della qualità delle acque sotterranee, ha supportato i miglioramenti pratici nei sistemi MAR e ha prodotto benefici in senso più ampio in idrogeologia. I pozzi di ricarica hanno largamente contribuito ad incrementare il ravvenamento degli acquiferi, in particolare nelle aree urbane e nella gestione delle acque di miniera. Negli ultimi anni sono state intraprese ricerche sulla governance, le pratiche operative, l’affidabilità, l’economicità, la valutazione del rischio e l’accettazione pubblica dei sistemi MAR. Dagli anni ‘60, la realizzazione di sistemi MAR è progredita ad un tasso del 5% all’anno, ma non sta tenendo il passo con l’aumento dei prelievi delle acque sotterranee. Attualmente si stima che i sistemi MAR forniscano circa 10 km3/anno, circa il 2.4% dei prelievi di acque sotterranee nei paesi che riportano la presenza di impianti MAR (o ~1.0% del prelievo globale di acque sotterranee). Si ritiene, sulla base dei dati provenienti dai paesi in cui l’uso di questa tecnica è avanzato, che i volumi immagazzinati attraverso i sistemi MAR potranno arrivare a superare il 10% dei prelievi globali, sostenendo la disponibilità, affidabilità e qualità delle risorse idriche.The last 60 years has seen unprecedented groundwater extraction and overdraft as well as development of new technologies for water treatment that together drive the advance in intentional groundwater replenishment known as managed aquifer recharge (MAR). This paper is the first known attempt to quantify the volume of MAR at global scale, and to illustrate the advancement of all the major types of MAR and relate these to research and regulatory advancements. Faced with changing climate and rising intensity of climate extremes, MAR is an increasingly important water management strategy, alongside demand management, to maintain, enhance and secure stressed groundwater systems and to protect and improve water quality. During this time, scientific research—on hydraulic design of facilities, tracer studies, managing clogging, recovery efficiency and water quality changes in aquifers—has underpinned practical improvements in MAR and has had broader benefits in hydrogeology. Recharge wells have greatly accelerated recharge, particularly in urban areas and for mine water management. In recent years, research into governance, operating practices, reliability, economics, risk assessment and public acceptance of MAR has been undertaken. Since the 1960s, implementation of MAR has accelerated at a rate of 5%/year, but is not keeping pace with increasing groundwater extraction. Currently, MAR has reached an estimated 10 km3/year, ~2.4% of groundwater extraction in countries reporting MAR (or ~1.0% of global groundwater extraction). MAR is likely to exceed 10% of global extraction, based on experience where MAR is more advanced, to sustain quantity, reliability and quality of water supplies
Migrastatin Analogues Inhibit Canine Mammary Cancer Cell Migration and Invasion
BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: Our results showed that two of six fully synthetic analogues of migrastatin: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in vivo studies are required to verify this hypothesis