77 research outputs found
INHIBITION OF AUTOPHAGY INCREASES THE RESPONSE TO SUNITINIB IN CCRCC CELL LINES
No full textIntroduction: Renal cell carcinoma (RCC) represents about 3% of all cancers and is the kidney malignancy with the
highest mortality rate of urinary neoplasms. The most common subtype of RCC is clear cell RCC (ccRCC) that
accounts for 70-80% of RCC cases (1, 2). One third of cases presents metastasis at diagnosis with a 30% of disease recurrence for RCC patients undergoing surgery. Moreover, treatment with tyrosine kinase inhibitors in RCC subjects with advanced disease has not shown any advantage on overall survival (1). Therefore, research on new therapeutic targets focuses on molecules that can enhance therapy response. This is a crucial point to improve the management of RCC patient. The kidney cancer progression could be induced by the activation of autophagy, the biological process used by cancer cells to produce energy in hypoxic and acidic environment. Thus, the use of autophagy inhibitors could be considered as a novel antitumor therapy (3). In addition, there is emerging evidence that the use of autophagy inhibitors could sensitize cancer cells to anticancer drugs. Therefore, the combination of both tyrosine kinase and autophagy inhibitors could improve therapy response in ccRCC patients. Materials
and Methods: Combined treatment with the autophagy inhibitor (Chloroquine) and anti-tyrosine kinase (Sunitinib)
was performed in two different ccRCC cell lines (KJ29 and Caki-2). Cell growth was analyzed by Cell Tyter System
(Promega, Madison, WI, USA), culturing cells in presence of both Chloroquine and Sunitinib for 24 and 48 h. Cell density after different treatments of ccRCC cells was evaluated by using a phase-contrast microscope at 10× magnification. Apoptosis was analyzed by the Hoechst method. Apoptotic nuclei were observed by a fluorescence microscope at 50× magnification after cell treatment with chloroquine and sunitinib. Results and Discussion: We observed that the upregulation of miR501-5p in ccRCC tissues is associated with a poor prognosis for ccRCC patients (2). Moreover, the overexpression of this miR induced the activation of autophagy in ccRCC cells. Cancer cells might use autophagy to trap and destroy molecular drugs by lysosomal vesicles. Therefore, the inhibition of autophagy should restore drug response. Consistently, we have observed that pre-treatment with Chloroquine, an autophagy inhibitor, in KJ29 ccRCC cells potentiated the Sunitinib-induced inhibition of cell growth compared to Sunitinib used alone. This finding was confirmed treating Caki-2, another ccRCC cell line, with both Chloroquine and Sunitinib. Moreover, the double treatment with these molecules reduced cell density compared to Chloroquine or Sunitinib, individually applied. The reduction of cell proliferation induced by the inhibition of both autophagy and tyrosine kinase receptors is associated with stimulation of apoptosis. In fact, the formation of apoptotic nuclei in double treated ccRCC cells, compared to those treated with the single compound, was observed. These results show that the inhibition of autophagy increases the efficacy of Sunitinib by the activation of apoptosis in ccRCC
cells. Conclusion: These data suggest that the double treatment with both autophagy and tyrosine kinase inhibitors
could be considered as a new therapeutic approach for the treatment of ccRCC patients.
1 Greef B and Eisen T: Medical treatment of renal cancer: new horizons. Br J Cancer 115: 505-516, 2016.
2 Mangolini A, Bonon A, Volinia S, Lanza G, Gambari R, Pinton P, Russo GR, Del Senno L, Dell'Atti L and Aguiari
G: Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma. FEBS Open
Bio 4: 952-965, 2014.
3 Kimura T, Takabatake Y, Takahashi A and Isaka Y: Chloroquine in cancer therapy: a doubleedged sword of
autophagy. Cancer Res 73: 3-7, 2013
Diet of bottlenose dolphins (Tursiops truncatus) from the Gulf of Cadiz: Insights from stomach content and stable isotope analyses [Dataset]
No full textThe ecological role of species can vary among populations depending on local and regional differences in diet. This is particularly true for top predators such as the bottlenose dolphin (Tursiops truncatus), which exhibits a highly varied diet throughout its distribution range. Local dietary assessments are therefore critical to fully understand the role of this species within marine ecosystems, as well as its interaction with important ecosystem services such as fisheries. Here, we combined stomach content analyses (SCA) and stable isotope analyses (SIA) to describe bottlenose dolphins diet in the Gulf of Cadiz (North Atlantic Ocean). Prey items identified using SCA included European conger (Conger conger) and European hake (Merluccius merluccius) as the most important ingested prey. However, mass-balance isotopic mixing model (MixSIAR), using δ13C and δ15N, indicated that the assimilated diet consisted mainly on Sparidae species (e.g. seabream, Diplodus annularis and D. bellottii, rubberlip grunt, Plectorhinchus mediterraneus, and common pandora, Pagellus erythrinus) and a mixture of other species including European hake, mackerels (Scomber colias, S. japonicus and S. scombrus), European conger, red bandfish (Cepola macrophthalma) and European pilchard (Sardina pilchardus). These contrasting results highlight differences in the temporal and taxonomic resolution of each approach, but also point to potential differences between ingested (SCA) and assimilated (SIA) diets. Both approaches provide different insights, e.g. determination of consumed fish biomass for the management of fish stocks (SCA) or identification of important assimilated prey species to the consumer (SIA).The study was funded by Fundación Loro Parque, CEPSA (Compañía Española de Petroleos S.A.), EcoCet Project [CGL2011-25543] J.G. and R.dS. were funded by the Spanish Ministry of Economy and Competitiveness through the Severo Ochoa Programme for Centres of Excellence in R+D+I [SEV-2012-0262]. A.M. and L.N. were partly supported by the Portuguese Foundation for Science and Technology [SFRH/BPD/64889/2009 and SFRH/BD/51416/2011]. Project ECOBOGUE-P11RNM7467 was funded by “Consejería de Economía, Innovación y Ciencia – Junta de Andalucía.Peer reviewe
Preliminary results of organochlorines levels and biomarker responses in skin biopsies of the common bottlenose dolphins from the Adriatic sea (Mediterranean sea)
No full textThe main objective of this study was to apply a sensitive non-lethal “multi-trial-diagnostic–tool” in skin biopsy of common bottlenose dolphin (Tursiops truncatus), combining molecular biomarkers (western blot of CYP1A1, CYP2B) with analysis of OCs, in subcutaneous blubber, to evaluate the toxicological status of this odontocete species in the Adriatic Sea (Mediterranean Sea). The results of these analyses were compared with those obtained on samples collected in two other areas: the Strait of Gibraltar and the Sicily Channel. The multi-trial biomarker tool applied to skin biopsies underlined differences in OCs and molecular biomarker responses between genders (male greater than female) and among these three areas, revealing a lower toxicological stress in the bottlenose dolphins of the central Adriatic Sea
Impact of maritime traffic and whale-watching on apparent survival of bottlenose dolphins in the Strait of Gibraltar
No full textEste artículo contiene 10 páginas, 4 figuras, 1 tabla.1. The Strait of Gibraltar is an important habitat for cetaceans due to its high marine
productivity. However, it is also the second most navigated channel in the world,
subjecting cetaceans to a high level of vessel traffic, including an established
whale-watching fleet. Both maritime traffic and whale-watching activities have
been shown to impact the behaviour of cetaceans, but little is known about their
impact on the demography and dynamics of cetacean populations.
2. The aim of this study was to evaluate the impacts of both ferry traffic and whalewatching
vessels on the apparent survival probability of a bottlenose dolphin
(Tursiops truncatus) population that occurs in the Strait.
3. A Bayesian hierarchical mark–recapture modelling approach was applied to 8 years
of photo-identification data (2002–2009). Apparent annual survival probability
was negatively correlated with ferry traffic, which explained >70% of temporal
variation in survival, in contrast to whale-watching, the effect of which was almost
negligible. Despite these results, other natural and human-related factors are
likely to drive apparent survival in the study area.
4. Abundance increased between 2002 and 2005, and then decreased between
2006 and 2009, while local per-capita recruitment decreased from 2004 until the
end of the study period. These shifts correlated temporally with the construction
of a large harbour on the Moroccan coast, which increased maritime traffic significantly,
including a 40% increase in ferry traffic that regularly transited the Strait.
5. These results highlight the need to better understand the impact of maritime traffic
on the demography of the dolphin population in the Strait, in order to implement
evidence-based conservation regulations in a region of high cetacean
occurrence.Funds were partially provided by the Spanish Ministry of Economy
and Innovation (ref. CGL2009-08298), Loro Parque Foundation,
CEPSA, the Spanish Ministry of the Environment, Fundación
Biodiversidad and two EU LIFE programme grants (ref.
LIFE07NAT/E/000732 and LIFE02NAT/E/8610). R. de Stephanis was
supported by the Spanish Ministry of Economy and Competitiveness
(Severo Ochoa SEV2012-0262; Juan de la Cierva programme).Peer reviewe
Athanasii Kircheri E Soc. Jesu mundus subterraneus in XII libros digestus quo divinum subterrestris mundi opificium, mira ergasteriorum naturae in eo distributio, verbo pantamorphon Protei regnum, universae denique naturae majestas et divitiae summa rerum varietate exponuntur, abditorum effectuum causae acri indagine inquisitae demonstrantur, cognitae per artis et naturae conjugium ad humanae vitae necessarium usum vario experimentorum apparatu, necnon novo modo, et ratione applicantur.
No full textÉdition : Editio tertia, ad fidem scripti exemplaris recognita, & prioribus emendatior : tum ab auctore Româ submissis variis observationibus novisque figuris auctior
Date de création : M. DC. LXXVIII [1678]
Les 2 tomes sont précédés, chacun, d'un frontispice gravé sur cuivre, daté de 1665. Frontispice et pl. pour la plupart gr. par Theodor Dirck Matham et Anthoine Heeres Siourtsma d'après des dessins de Johann Paul Schor, H. Bonzon et Crispin de Passe. Portraits non signés de l'auteur et du dédicataire, le pape Alexandre VII.
Porte la mention : "Cum Privilegiis"
Signatures : *⁴ 2*⁶ A-2Z⁴ 3A² (volume 1)
Signatures : *⁴ A-2Z⁴ 3A-3R⁴ 3S⁶ (volume 2)
Empreinte :
e,ue m.n- æ-is umin (3) 1678 (R) (volume 1)
insi a.o- neo- tiAt (3) 1678 (R) (volume 2)
Propriété et historique de la conservation :
Ex-libris "Bibliothecæ Averbodianæ Apposius Rmus D. Stephanis Abbas 1701"
Identification de l'exemplaire :
Les pages 7 à 10 sont manquantes dans le tome 1
Reliure : Reliure de veau brun estampée à froi
Petri Rosseti Stephanis siue epos de beatissimi protomartyris Stephani Agone.
No full textDrukkersmerk op titelbladDatum in colofon, idus Martias M.D.XVI.Machiels, J. Catalogus van de boeken gedrukt vóór 1600 ; R 279Renouard, P. Josse Badius Ascensius III, p. 218-219 ; Renouard, Ph. Imprimeurs II nr. 337Europeana-GoogleBooksVergauwen, Fran
Valutazione dello stato tossicologico del tursiope (Tursiops truncatus) nel Mar Mediterraneo e nel Golfo di California (Mar di Cortez-Messico) mediante l'utilizzo della biopsia cutanea
No full textPCB pollution continues to impact populations of orcas and other dolphins in European waters
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Ecotoxicological status of Tursiops truncatus in the Mediterranean Sea and in the Gulf of California (Sea of Cortez-Mexico) using skin biopsy as diagnostic tool
No full textThe main objective of this study was to apply a sensitive nonlethal “multi-trial-diagnostic-tool” in skin biopsy of common bottlenose dolphin (Tursiops truncatus), combining molecular biomarkers, such as two isoforms of the cytochrome P450 (CYP1A1 e CYP2B) with analysis of lipophilic contaminants, such as hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDTs), polychlorobyphenils (PCBs) and polycyclic aromatic hydrocarbons (PAHs), to evaluate the toxicological status of this odontocete in 4 Mediterranean areas (Isle of Vis; Isle of Lampedusa; Isle of Asinara; and Strait of Gibraltar) and in the Sea of Cortez (Mexico). These surveys allowed to estimate the “toxicological stress” of the specimens of the different populations, in particular considering that the Sea of Cortez (Mexico) is a remote area and therefore exposed to a significantly lower anthropic pressure than the Mediterranean Sea. The results of this study reveal that the bottlenose dolphin population most affected by OCs and PAHs contamination is the one sampled in the Strait of Gibraltar. In the specimens of this area the highest levels of CYP1A1 were also found. Lower levels of OCs were found in the specimens sampled in the Sea of Cortez where, however, the highest levels of CYP2B were detected. The lowest average values of PAHs were measured in skin biopsies of the specimens sampled in the Adriatic area and in the area of the Isle of Asinara. In conclusion this preliminary data suggest the potential application of the proposed diagnostic approach as a powerful method to define the toxicological status of this marine top predator and suggest the application of this methodology in the future EU Marine Strategy
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