Infrequent loss of luminal differentiation in ductal breast cancer metastasis

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and -positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes

T cells isolated from G-CSF-treated multiple myeloma patients are suitable for the generation of BCMA-directed CAR-T cells

Autologous cell immunotherapy using B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells is an effective novel treatment for multiple myeloma (MM). This therapy has only been used for relapsed and refractory patients, at which stage the endogenous T cells used to produce the CAR-T cells are affected by the immunosuppressive nature of advanced MM and/or side effects of previous therapies. An alternative pool of fitter T cells is found in leukocytoapheresis products that are routinely collected to obtain hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) early in the treatment of MM. However, to mobilize the progenitor cells, patients are dosed with granulocyte colony-stimulating factor (G-CSF), which is reported to adversely affect T cell proliferation, function, and differentiation. Here, we aimed to first establish whether G-CSF treatment negatively influences T cell phenotype and to ascertain whether previous exposure of T cells to G-CSF is deleterious for anti-BCMA CAR-T cells. We observed that G-CSF had a minimal impact on T cell phenotype when added in vitro or administered to patients. Moreover, we found that CAR-T cell fitness and anti-tumor activity were unaffected when generated from G-CSF-exposed T cells. Overall, we showed that ASCT apheresis products are a suitable source of T cells for anti-BCMA CAR-T cell manufacture

Discards and impact associated with wedge clam fisheries in the Alboran Sea: composition, structure and spatio-temporal variability

The present study describes the composition, structure and damage caused by mechanized dredges on discarded species from the wedge clam (Donax trunculus Linnaeus 1758) fisheries in the Alboran Sea. Discard samples were collected on board artisanal fishing vessels in 95 commercial hauls performed in Fuengirola and Caleta de Vélez between March 2013 and March 2014. The collected fauna was characterized according to their abundance and biomass, and considering their damage type by using a three-level scale (no damage, intermediate damage and severe damage) defined for the different faunal groups identified. Data was analysed for contrasting variations in the different areas and seasons. A total of 87 species were identified, including Paguridae and Annelida. Molluscs were the best represented faunal group, followed by decapod crustaceans and echinoderms. Other groups did not usually exceed 1% of the total abundance and biomass such as fishes or sipunculids. Most discarded individuals displayed no damage after their capture, promoting therefore a high survival rate. Among the dominant taxa, echinoderms and crustaceans displayed the highest proportion of damaged individuals due to their fragile exoesqueletons, which make them to be highly vulnerable to the physical impact caused by mechanized dredges and the further processing on board.Versión del edito

Analysis of discards and benthic impact of mechanized dredges fishery of the stripped venus clam in the Alboran Sea

This study describes the composition and structure of discards of the stripped venus clam (Chamelea gallina) fishery, and the damage caused by mechanized dredges on discarded species in the Alboran Sea. A total of 106 commercial fishing hauls have been analyzed between March 2013 and March 2014. Samples were collected on board artisanal fishing vessels based in Fuengirola and Caleta de Vélez harbours (Málaga). The collected fauna was characterized considering the damage presented by using a three level scale: no damage, intermediate damage and severe damage. Quantitative and qualitative data were analyzed with multivariate methods for contrasting seasonal variability. A total of 98 species were identified, with molluscs being the best-represented taxa (e.g. Acanthocardia tuberculata, Mactra stultorum), followed by decapod crustaceans (e.g. Portumnus latipes, Liocarcinus vernalis) and echinoderms (e.g. Echinocardium cf. mediterraneum, Ophiura ophiura). Most individuals displayed no damage after their capture. Echinoderms displayed the highest proportion of damaged individuals, followed by mollucs and decapod crustaceans. The discard structure and damage on non-target species displayed significant seasonal differences, with the higher proportions of damaged individuals in winter.Versión del edito

First record of the starfish Luidia atlantidea Madsen, 1950 in the Mediterranean Sea, with evidence of persistent populations

The starfish Luidia atlantidea, an echinoderm known hitherto from infralittoral and circalittoral bottoms of the northwestern African coasts, is reported for the first time in the European margin and in the Mediterranean Sea. A total of 31 specimens of different sizes (disc diameters from 0.8 to 2.9 cm) were collected from the mechanized dredges fleet targeting four commercial bivalves (Acanthocardia tuberculata, Callista chione, Chamelea gallina, Donax trunculus) between February and July 2013 in the northern Alboran Sea (southern Spain). Most individuals had broken arms due to the collecting gear. The specimens were generally collected in low numbers, at shallower depths (1-11 m) than the bathymetric range reported for this species along the northwestern African coasts (10-80 m). The data provided here, and supported by old specimens collected between 1980-1990, suggests that local populations of L. atlantidea occur in shallow infralittoral soft bottoms of the northern Alboran Sea. This constitutes a new extended northeastern limit for the distribution of L. atlantidea and increases the known number of Luidia species in the Mediterranean Sea.Postprint0,708

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever

Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. The incidence of NF among the groups was reduced (64%, 44%, and 24%; P2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age �60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05. G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial

Biodiversity Assessment and Geographical Affinities of Discards in Clam Fisheries in the Atlantic–Mediterranean Transition (Northern Alboran Sea)

This study focused on the assessment and quantification of discards generated by clam fisheries along the northern Alboran Sea (western Mediterranean). Discard samples (n = 278) were collected throughout one year on board nine commercial vessels. A total of 129 species were identified, mostly represented by molluscs (72 spp.), arthropods (20 spp.) and echinoderms (12 spp.). Molluscs dominated in terms of abundance (67.5%) and biomass (94.2%). The superfamily Paguroidea (i.e. hermit crabs), together with undersized target individuals, were the most abundant taxa. The abundance and biomass of discards displayed significant maximum values in winter, which could be partly related to biotic factors including population dynamics of some dominant species. Multivariate analyses indicated the presence of different assemblages related to the targeted bivalve species, reflecting the transition between a fine surface-sands biocoenosis exposed to wave action and a well-sorted fine sands biocoenosis below 5 m depth. Analysis of biogeographical affinities showed that most discarded species (73.2%) have an extensive Atlantic range, whereas 7.1% have a restricted distribution within the Mediterranean. The presence of subtropical species highlights the uniqueness of this area (the Atlantic–Mediterranean transition) in European seas. The usefulness of discard analysis for biodiversity assessment is discussed.Postprin

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells