Sortilin-related receptor is a druggable therapeutic target in breast cancer.

In breast cancer, the currently approved anti-receptor tyrosine-protein kinase erbB-2 (HER2) therapies do not fully meet the expected clinical goals due to therapy resistance. Identifying alternative HER2-related therapeutic targets could offer a means to overcome these resistance mechanisms. We have previously demonstrated that an endosomal sorting protein, sortilin-related receptor (SorLA), regulates the traffic and signaling of HER2 and HER3, thus promoting resistance to HER2-targeted therapy in breast cancer. This study aims to assess the feasibility of targeting SorLA using a monoclonal antibody. Our results demonstrate that anti-SorLA antibody (SorLA ab) alters the resistance of breast cancer cells to HER2 monoclonal antibody trastuzumab in vitro and in ovo. We found that SorLA ab and trastuzumab combination therapy also inhibits tumor cell proliferation and tumor cell density in a mouse xenograft model of HER2-positive breast cancer. In addition, SorLA ab inhibits the proliferation of breast cancer patient-derived explant three-dimensional cultures. These results provide, for the first time, proof of principle that SorLA is a druggable target in breast cancer.

Enhanced threat of tick-borne infections within cities? Assessing public health risks due to ticks in urban green spaces in Helsinki, Finland.

Most tick-related studies in Europe have been conducted in nonurban areas, but ticks and tick-borne pathogens also occur in urban green spaces. From a public health perspective, risks regarding tick-borne infections should be studied in these urban areas, where contacts between infected ticks and humans may be more frequent than elsewhere, due to high human activity. We examined the risk of encountering an infected tick in urban green spaces in Helsinki, Finland. We collected ticks at nine sites throughout Helsinki, recorded the prevalence of several pathogens and identified areas with a high potential for contacts between infected ticks and humans. Moreover, we explored the relationship between the density of Borrelia burgdorferi sensu lato-infected ticks and locally diagnosed cases of borreliosis and compared the potential for human-tick encounters in Helsinki to those in nonurban areas in south-western Finland. During 34.8 km of cloth dragging, 2,417 Ixodes ricinus were caught (402 adults, 1,399 nymphs and 616 larvae). From analysed nymphs, we found 11 distinct tick-borne pathogens, with 31.5% of nymphs carrying at least one pathogen. Tick activity was highest in August and September, leading to the density of nymphs infected with B. burgdorferi s.l., and concurrently infection risk, to also be highest during this time. Nymph densities varied between the sampling sites, with obvious implications to spatial variation in infection risk. While ticks and tick-borne pathogens were found in both Helsinki and nonurban areas in south-western Finland, the estimates of human activity were generally higher in urban green spaces, leading to a higher potential for human-tick contacts therein. The presence of ticks and tick-borne pathogens and high local human activity in urban green spaces suggest that they form potential foci regarding the acquisition of tick-borne infections. Risk areas within cities should be identified and knowledge regarding urban ticks increased.

Monitoring of ticks and tick-borne pathogens through a nationwide research station network in Finland.

In 2015 a long-term, nationwide tick and tick-borne pathogen (TBP) monitoring project was started by the Finnish Tick Project and the Finnish Research Station network (RESTAT), with the goal of producing temporally and geographically extensive data regarding exophilic ticks in Finland. In the current study, we present results from the first four years of this collaboration. Ticks were collected by cloth dragging from 11 research stations across Finland in May-September 2015-2018 (2012-2018 in Seili). Collected ticks were screened for twelve different pathogens by qPCR: Borrelia afzelii, Borrelia garinii, Borrelia valaisiana, Borrelia burgdorferi sensu stricto, Borrelia miyamotoi, Babesia spp., Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis, Francisella tularensis, Bartonella spp. and tick-borne encephalitis virus (TBEV). Altogether 15 067 Ixodes ricinus and 46 Ixodes persulcatus were collected during 68 km of dragging. Field collections revealed different seasonal activity patterns for the two species. The activity of I. persulcatus adults (only one nymph detected) was unimodal, with activity only in May-July, whereas Ixodes ricinus was active from May to September, with activity peaks in September (nymphs) or July-August (adults). Overall, tick densities were higher during the latter years of the study. Borrelia burgdorferi sensu lato were the most common pathogens detected, with 48.9 ±â€¯8.4% (95% Cl) of adults and 25.3 ±â€¯4.4% of nymphs carrying the bacteria. No samples positive for F. tularensis, Bartonella or TBEV were detected. This collaboration project involving the extensive Finnish Research Station network has ensured enduring and spatially extensive, long-term tick data collection to the foreseeable future.