Abemaciclib: A CDK4/6 inhibitor for the treatment of HR+/HEeR2- advanced breast cancer

Although early breast cancer (BC) is highly curable, advanced or metastatic disease poses numerous challenges in terms of medical management and treatment decisions and is associated with significantly worse prognosis. Among the new targeted agents, anticancer drugs exploiting the cell-cycle machinery have shown great potential in preclinical studies. CDK4/6 inhibitors target the cyclin D/CDK/retinoblastoma signaling pathway, inducing cell-cycle arrest, reduced cell viability and tumor shrinking. As the cyclin D/CDK complex is activated downstream of estrogen signaling, the combination of CDK4/6 inhibitors with standard endocrine therapies represents a rational approach to elicit synergic antitumor activity in hormone receptor-positive BC. The results of clinical trials have indeed confirmed the superiority of the combination of CDK4/6 inhibitors plus endocrine therapies over endocrine therapy alone. Currently approved are three compounds that exhibit similar structural characteristics as well as biological and clinical activities. Abemaciclib is the latest CDK4/6 inhibitor approved by the US Food and Drug Administration (FDA) in view of the results of the MONARCH 1 and 2 trials. Further trials are ongoing as other important questions await response. In this review, we focus on abemaciclib to examine preclinical and clinical results, describing current therapeutic indications, open questions and ongoing clinical trials

Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma

Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16(INK4A), blocking thereby MM cell cycle at G1. Future randomised phase III studies with CDK4/6 inhibitors in MM carrying relevant CDK4/6, cyclin D1/3 or p16 aberrations will be warranted

Corticosteroid switch after progression on abiraterone acetate plus prednisone

Introduction: Abiraterone acetate plus prednisone is approved in metastatic castration-resistant prostate cancer. There is some evidence in favour of the steroid switch from prednisone to dexamethasone in patients who progressed whilst on abiraterone acetate plus prednisone or prednisolone. Materials and Methods: The aim of this review is to discuss the results from the clinical studies available, examining potential mechanisms of action and patient selection criteria for this treatment option. Results: A total of four studies were evaluated. Among possible eligibility criteria for steroid switch, we found: PSA progression without any radiological or clinical progression during abiraterone acetate + prednisone; no high-grade adverse events related to CYP-17 inhibition; and unfitness for chemotherapy or radium-223. Conclusion: Although large randomized prospective trials are warranted, steroid switch seems to offer a good option for certain patients treated with abiraterone acetate plus prednisone or prednisolone

Support of multispectral very high solution remotely sensed imagery for old-growth beech forest detection.

In the Mediterranean basin human activity has modified landscapes for millennia,nevertheless there are few remote forest areas relatively untouched long enough from direct anthropogenic disturbance to develop old-growth attributes. The aim of this note is to assess the potential of QuickBird (QB) satellite multispectral imagery for detecting old-growth forest stands, considering as case study a Mediterranean beech forest in central Italy. The segmentation-based analysis of QB image proved to be a promising tool to detect scaledependent pattern of forest structural heterogeneity. Values of remotely sensed attributes are compared in old-growth and not-old-growth stands: the statistical analysis showed that oldgrowthness is associated to the variability of multispectral reflectance from the image objects (polygons). Green band variability, notably, expressed by Ratio_band_2 has proven to be helpful for predicting old-growthness

[1,2,3]triazolo[4,5-<i>H</i>]chinoloni: una nuova classe di promettenti chemioterapici antitubercolari

Alcuni acidi triazolo[4,5-h] e [4,5-f]chinoloncarbossilici angolari, sintetizzati in precedenza come antiinfettivi del tratto urinario, hanno mostrato interessanti valori di MIC90 nei confronti di M. tuberculosis H37Rv. Allo scopo di approfondire le nostre conoscenze sui rapporti struttura-attività di questa classe, abbiamo pertanto preparato una nuove serie di derivati

Is there still a place for vinorelbine in advanced metastatic castration resistant prostate cancer?

The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60\u200amg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels 6550% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treate

Decomposition and biological colonization of native and exotic leaf litter in a Central Spain stream

Riparian invasion by exotic trees may lead to changes in the quality of leaf-litter inputs to freshwater ecosystems. Leaflitter inputs are especially important in headwater streams, where aquatic food webs largely depend on the organic matter provided by the terrestrial vegetation. In a headwater stream of Central Spain, North of Guadalajara Province (Tagus basin) we compared the decomposition and biological colonization of leaf litter among two exotic (Ailanthus altissima Mill. Swingle and Robinia pseudoacacia L.) and two native trees (Fraxinus angustifolia Vahl. and Populus alba L.) co-existing in riparian zones. We hypothesized a lower biological colonization of exotic leaves due to organisms have not co-evolved with the exotic trees according to the Novel Weapons Hypothesis (NWH) and, consequently, lower decomposition rates of exotic leaves. To test our hypothesis, litter bags with different mesh sizes (coarse (C) and fine (F)), were used to distinguish between the total and microbial decomposition. The litter bags were placed in the stream and recovered after 2, 20, 39, 62 and 82 days of incubation. After each collection, we assessed the amount of remaining litter, analysed the nitrogen (N) and phosphorous (P) in the litter, identified the macroinvertebrates and quantified the fungal biomass. Consistent with our hypothesis, we found greater fungal biomass buildup on native leaves than on exotic leaves. However, decomposition rates (k) were species-specific, being the ranking in C-bags (A. altissima = F. angustifolia > P. alba > R. pseudoacacia) slightly different than in F-bags (A. altissima > F. angustifolia > P. alba > R. pseudoacacia). The k in both the C-bags and F-bags were correlated with leaf traits, such as lignin, acid detergent fibre (ADF) and lignin:P. There was not a clear effect of the exotic species on macroinvertebrate variables, but the contribution of macroinvertebrates to litter decomposition was lower in exotic litter than in native litter, as shown by a lower ratio between k in C-bags and k in F-bags (kC : kF). Our results supported that invasive species might impact both biological colonization and decomposition rates in stream ecosystems by the addition of different quality leaf litter when compared to native vegetation. The differences in the biological colonization may be explained by the NWH, but differences in the decomposition rates were better explained by litter quality

On the presence of a complex hybrid fish (Squalius alburnoides Steindachner, 1866) in a cave system located in southern of Spain

Ponencia Invitada Inaugural del Congreso de Espeleología "EspeleoMeeting Ciudad de Villacarrillo" (Villacarrillo (Jaén), 13, 14 y 15 de agosto de 2016).[ES] En este trabajo se describe a través de la citología, histología y secuenciación del gen de la rodopsina, la única población de peces encontrada en una cueva de la Península Ibérica. Esta población pertenece a la especie Squalius alburnoides (Steindachner, 1866) (Cyprinidae) y tiene la particularidad de tener un origen híbrido con individuos y poblaciones de diferentes ploidias (2n=50; 3n=75 y 4n=100) y distintos mecanismos de reproducción. Los peces de la cueva de Peal del Becerro I presentaron una degeneración incipiente de la retina, con menor cantidad de fotorreceptores y pigmentación que los peces de la misma especie situados en el exterior de la cueva (Embalse de La Bolera). Todos resultaron ser tetraploides simétricos AAPP lo que sugiere que este biotipo favorece de algún modo la viabilidad de poblaciones de esta especie permitiendo recuperar la bisexualidad y un genoma balanceado. Sin embargo, es necesario realizar estudios en profundidad desde la genómica y transcriptómica y tener un mejor conocimiento de la biología y ecología de esta población cavernícola.[EN] In this study we described through a multidisciplinary approach (cytology, histology and rhodopsin gene sequencing) the only cave population of freshwater fish found in the Iberian Peninsula. This population belong to the species Squalius alburnoides (Steindachner, 1866) (Cyprinidae), which has the singularity of being a species of hybridogenetic origin with individuals and populations of different ploidies (2n=50; 3n=75 y 4n=100) and diverse mechanisms of reproduction. The individuals of S. alburnoides found in the Peal del Becerro I cave showed an incipient degeneration of the retina, with lower amount of photoreceptor cells and pigmentation relative to individuals outside the cave (de la Bolera reservoir). All individuals from the cave were symmetric tetraploids AAPP, which suggests that this biotope is favouring the viability of this population through the recovery of bisexuality and a balanced genome. Nonetheless, further deeper studies using genomics and transcriptomics approaches are required to achieve a better understanding of the biology and ecology of this cave-dweller population.Peer reviewe