Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.     

Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model

Objective. In this in vivo study, we investigated changes in the proteins that coat monosodium urate (MSU) crystals in human synovial fluid samples and rat air pouch fluid samples obtained sequentially during periods of active and resolving inflammation, in order to evaluate whether in vivo findings are consistent with hypotheses on roles of protein coating based on in vitro findings. Methods. Crystals from patients with gout were isolated from joint fluids with acute inflammation, and subsequently from the same joints at the time inflammation was resolving. Crystals were also obtained using the rat subcutaneous air pouch model. Immunogold was used to label proteins coating MSU crystals, for light microscopy (LM) and transmission electron microscopy (TEM) studies. Results. Dense immunogold–silver labeling for IgG was observed under LM on crystals from fluid with acute inflammation, whereas other proteins (apolipoproteins [Apo], fibronectin, fibrinogen, albumin) were not labeled significantly. Apo B became strongly positive on crystals as the inflammation subsided, whereas other proteins were only weakly positive and IgG became absent or weakly positive. Quantitative TEM evaluation confirmed the LM observations. Conclusion. This study provides the first in vivo evidence supporting the notion derived from previous in vitro studies that proteins coating MSU crystals change as inflammation evolves. Protein coatings may play an important role in the self-limited nature of gouty inflammation. IgG coating MSU crystals may enhance the inflammation. As the inflammation subsides, Apo B could displace the IgG by competitively coating sites on crystals and could contribute in part to the resolution of the acute gouty arthritis.     

Nasal response to stress test in healthy subjects: an experimental pilot study

European Archives of Oto-Rhino-Laryngology - Stress has been suspected to play a role in rhinitis. The role of stress on nasal patency has been not yet elucidated. The aim was to evaluate the...     

Associations of Maternal Consumption of Dairy Products during Pregnancy with Perinatal Fatty Acids Profile in the EDEN Cohort Study

Maternal diet is the main source of fatty acids for developing offspring in-utero and in breastfed infants. Dairy products (DP) are important sources of fat in the European population diet. C15:0 and C17:0 fatty acids have been suggested as biomarkers of dairy fat consumption. This study’s aim is to describe the associations between maternal DP (milk included) consumption during pregnancy and C15:0, C17:0 and polyunsaturated fatty acid (PUFA) levels in perinatal biofluids. Study populations were composed of 1763, 1337 and 879 French mothers from the EDEN (“Étude des Déterminants pre- et post-natals de la santé de l’ENfant”) study, with data on maternal and cord red blood cells’ (RBC) membrane and colostrum, respectively. Associations were assessed using linear regression models adjusted for recruitment center, maternal age, healthy dietary pattern or fish consumption. Greater adherence to a ”cheese” consumption pattern was associated with lower linoleic acid level in colostrum and higher C15:0 and C17:0 levels but in a less consistent manner for C17:0 across biofluids. Greater adherence to “semi-skimmed milk, yogurt” and “reduced-fat DP” patterns was related to higher docosahexaenoic acid and total n-3 PUFA levels and lower n-6/n-3 long-chain PUFA ratio in maternal and cord RBC. Our results suggest that C15:0 could be a good biomarker of maternal dairy fat consumption in perinatal biofluids.     

Analytical Sensitivity of Six SARS-CoV-2 Rapid Antigen Tests for Omicron versus Delta Variant

Rapid antigen detection (RAD) tests are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC), presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One hundred and twenty samples were selected and tested with both RT-qPCR and six commercial RAD tests that are commonly sold in Belgian pharmacies. Of these, direct whole-genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron (BA.1 and BA.1.1 sub-lineages, respectively). The sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) ranged from 70.0% to 92.9% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct > 25, corresponding to <4.9 log₁₀ copies/mL), only the Roche RAD test showed acceptable performances for the Delta strains (80.0%), while poor performances were observed for the other RAD tests (20.0% to 40.0%). All the tested devices had poor performances for the Omicron samples with a low viral load (0.0% to 23.1%). The poor performances observed with low viral loads, particularly for the Omicron strain, is an important limitation of RAD tests, which is not sufficiently highlighted in the instructions for use of these devices.     

The bacteriology of hidradenitis suppurativa: a systematic review

Hidradenitis suppurativa (HS) is a chronic inflammatory disabling skin disease consisting of recurrent nodules, sinuses, fistulas and scarring involving the intertriginous regions. HS is often a therapeutic challenge and most treatments are off‐label. A better understanding of aetiology and pathogenesis of HS may facilitate the development of effective treatment. Although the clinical presentation is strongly reminiscent of bacterial infection, the role of bacteria remains controversial. Studies have isolated an array of different bacteria specimens. Consistent findings of Gram‐positive cocci and Gram‐positive rods including Staphylococus aureus, coagulase‐negative staphylococci (CoNS) and Corynebacterium species in deep tissue samples have been demonstrated in HS and may constitute a central target for the immune system. Efficacy of antibiotics, that is rifampicin, clindamycin or tetracycline, supports a microbial role in disease pathogenesis. However, these antibiotics also work as immunomodulators of especially T cells, and the underlying mechanisms may therefore be more complex. We performed a systematic review of previous studies investigating the bacterial flora in hidradenitis suppurativa. We searched PubMed, EMBASE, Royal Danish Library and Cochrane library (search date 11 December 2014). A total of 66 papers were identified and nine papers published between 1988 and 2014 matched our inclusion criteria, yielding bacteriological data of a total of 324 patients with HS (mean age 36.8 years and female/male ratio 215/109). This overview of the bacteriology may aid researchers and physicians exploring the potential role of bacteria in HS. Furthermore, to stimulate a broader debate, we also present different viewpoints on the possible role of bacteria in HS.