Targeting RANKL in metastasis

Acting through its cognate receptor, receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) is an essential mediator of osteoclast function and survival. Preclinical data have now firmly established that blockade of tumor-induced osteoclastogenesis by RANKL inhibition will not only protect against bone destruction but will also inhibit the progression of established bone metastases and delay the formation of de novo bone metastases in cancer models. In patients with bone metastases, skeletal complications are driven by increased osteoclastic activity and may result in pathological fractures, spinal cord compression and the need for radiotherapy to the bone or orthopedic surgery (collectively known as skeletal-related events (SREs)). Denosumab, a fully human monoclonal antibody against RANKL, has been demonstrated to prevent or delay SREs in patients with solid tumors that have metastasized to bone. In addition to its central role in tumor-induced osteolysis, bone destruction and skeletal tumor progression, there is emerging evidence for direct pro-metastatic effects of RANKL, independent of osteoclasts. For example, RANKL also stimulates metastasis via activity on RANK-expressing cancer cells, resulting in increased invasion and migration. Pharmacological inhibition of RANKL may also reduce bone and lung metastasis through blockade of the direct action of RANKL on metastatic cells. This review describes these distinct but potentially overlapping mechanisms by which RANKL may promote metastases

Els textos pusissimers barcelonesos de 1415-1432 en el manuscrit 35 del Monestir de Poblet

El Dr. Josep Perarnau va publicar a l’Arxiu de Textos Catalans Antics 3 (1984) 58-191 uns escrits teològics medievals en favor de l’extensió universal de la festa de la Immaculada Concepció. Per a la seva edició va recórrer a diversos manuscrits d’arreu d’Europa sense haver arribat a conèixer el manuscrit núm. 35 del monestir de Poblet, que conté els textos esmentats. Aquí s’ofereix la descripció codicològica d’aquest manuscrit i també la col·lació de totes les seves variants de lectura respecte al text establert aleshores

Scientific, Technical and Economic Committee for Fisheries (STECF) - Fisheries Dependent Information – FDI (STECF-20-10)

Commission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4–10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar disciplines. The STECF reviewed the report of the EWG on Fisheries-dependent Information during its winter 2020 virtual plenary meeting.E