Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.</p> <p>Methods</p> <p>HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence <it>in situ </it>hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.</p> <p>Results</p> <p>Median time to progression and overall survival were 9 (range 2 - 54) and 20 (range 3 - 101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (<it>p </it>= 0.05) and higher stage (<it>p </it>= 0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53 ± 10.21 vs 2.50 ± 4.12, <it>p </it>= 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (<it>p </it>= 0.046). p53 expression was only associated with higher stage disease (<it>p </it>= 0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.</p> <p>Conclusion</p> <p>Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.</p

Effects of CreERT2, 4-OH Tamoxifen, and Gender on CFU-F Assays

Gene function in stem cell maintenance is often tested by inducing deletion via the Cre-loxP system. However, controls for Cre and other variables are frequently not included. Here we show that when cultured in the presence of 4-OH tamoxifen, bone and marrow cells containing the CreERT2 construct have a reduced colony forming ability. Inactive CreERT2 recombinase, however, has the opposite effect. Young female marrow cells containing the inactive CreERT2 construct grew more colonies than cells lacking the construct altogether. Young female control marrow cells (i.e., negative for CreERT2) also produced significantly greater colony numbers when cultured with 4-OH tamoxifen, compared with the ethanol vehicle control. In conclusion, we report that the use of the Cre-loxP system is inadvisable in combination with CFU-F assays, and that appropriate controls should be in place to extend the future use of Cre-loxP in alternate assays

Commercial products for osteochondral tissue repair and regeneration

The osteochondral tissue represents a complex structure composed of four interconnected structures, namely hyaline cartilage, a thin layer of calcified cartilage, subchondral bone, and cancellous bone. Due to the several difficulties associated with its repair and regeneration, researchers have developed several studies aiming to restore the native tissue, some of which had led to tissue-engineered commercial products. In this sense, this chapter discusses the good manufacturing practices, regulatory medical conditions and challenges on clinical translations that should be fulfilled regarding the safety and efficacy of the new commercialized products. Furthermore, we review the current osteochondral products that are currently being marketed and applied in the clinical setting, emphasizing the advantages and difficulties of each one.FROnTHERA (NORTE-01-0145- FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The authors would also like to acknowledge H2020-MSCA-RISE program, as this work is part of developments carried out in BAMOS project, funded by the European Union’s Horizon 2020 research and innovation program under grant agreement N° 734156. The financial support from the Portuguese Foundation for Science and Technology under the program Investigador FCT 2012 and 2015 (IF/00423/2012 and IF/01285/2015)info:eu-repo/semantics/publishedVersio

Bibliografía sobre “Aspectos históricos, sociales, económicos, legales de la Pesca Argentina”

La siguiente bibliografía se realiza a modo de cumplimentar el trabajo final de la cátedra Bibliografía y Selección de Textos. El siguiente repertorio bibliográfico tiene como fin facilitar el acceso y localización del material sobre aspectos históricos, económicos, legales y sociales de la Pesca en la Argentina. Dicho trabajo fue elaborado para satisfacer las necesidades de la Biblioteca de INIDEP, ya que es de su interés la recopilación de todo el material dentro de una misma bibliografía. El objetivo de esta compilación es satisfacer la creciente demanda de los usuarios de dicha biblioteca, dentro del grupo de usuarios encontramos: científicos, biólogos, oceanógrafos, veterinarios, empresarios, pesqueros, alumnos de diferentes carreras, como Biología, Geografía, Economía; incluyendo además, alumnos del tercer ciclo de EGB. (PDF tiene 61 paginas.

Forest dormouse (Dryomys nitedula) populations in southern Italy belong to a deeply divergent evolutionary lineage. Implications for taxonomy and conservation

The Forest Dormouse (Dryomys nitedula) is a small rodent with a wide, albeit severely fragmented distribution, ranging from central Europe to central Asia. Within the Italian region, D. nitedula populations are restricted to forested mountain areas of two largely disconnected regions, the eastern Alps and the Calabria region, where two distinct subspecies (D. nitedula intermedius and D. nitedula aspromontis, respectively) have been described on the basis of phenotypic characters (i.e., fur colour). Here we analysed D. nitedula samples from both regions, to investigate patterns of genetic divergence and phylogenetic relationship among these two populations. Genetic variation was studied at the level of one mitochondrial (cytochrome b gene) and three nuclear gene fragments (exon1 of the interstitial retinoid-binding protein, exon 10 of the growth hormone receptor, and re- combination activating gene 1). Phylogenetic analyses were performed using Maximum Likelihood and Bayesian inference methods. D. n. aspromontis and D. n. intermedius were found to be reciprocally monophyletic in all the phylogenetic analyses, and the genetic divergence observed between them at the mitochondrial CYTB gene was conspicuous (HKY: 0.044) when compared to previously observed values among many sister species of rodents. Our results clearly show that D. nitedula aspromontis is a deeply divergent, narrow endemic evolutionary lineage, and its conservation needs should be carefully evaluated in the near future. Moreover, such deep genetic divergence, together with phenotypic differentiation between D. n. intermedius and D. n. aspromontis, suggest that D. nitedula populations in southern Italy might belong to a distinct, previously unrecognized species