Karlssonpowell1959

Treatment options for triple-negative breast cancer remain limited. Activation of the PI3K pathway via loss of PTEN and/or INPP4B is common. Buparlisib is an orally bioavailable, pan-class I PI3K inhibitor. We evaluated the safety and efficacy of buparlisib in patients with metastatic triple-negative breast cancer.

This was a single-arm phase 2 study enrolling patients with triple-negative metastatic breast cancer. Patients were treated with buparlisib at a starting dose of 100 mg daily. The primary endpoint was clinical benefit, defined as confirmed complete response (CR), partial response (PR), or stable disease (SD) for ≥ 4 months, per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. A subset of patients underwent pre- and on-treatment tumor tissue biopsies for correlative studies.

Fifty patients were enrolled. Selleckchem Lenalidomide Median number of cycles was 2 (range 1-10). The clinical benefit rate was 12% (6 patients, all SD ≥ 4 months). Median PFS was 1.8 e observed. Downmodulation of key nodes in the PI3K pathway was observed in patients who achieved SD. PI3K pathway inhibition alone may be insufficient as a therapeutic strategy for triple-negative breast cancer.

NCT01790932 . Registered on 13 February 2013; NCT01629615 . Registered on 27 June 2012.

NCT01790932 . Registered on 13 February 2013; NCT01629615 . Registered on 27 June 2012.

With the "Artemis"-mission mankind will return to the Moon by 2024. Prolonged periods in space will not only present physical and psychological challenges to the astronauts, but also pose risks concerning the medical treatment capabilities of the crew. So far, no guideline exists for the treatment of severe medical emergencies in microgravity. We, as a international group of researchers related to the field of aerospace medicine and critical care, took on the challenge and developed a an evidence-based guideline for the arguably most severe medical emergency - cardiac arrest.

After the creation of said international group, PICO questions regarding the topic cardiopulmonary resuscitation in microgravity were developed to guide the systematic literature research. Afterwards a precise search strategy was compiled which was then applied to "MEDLINE". Four thousand one hundred sixty-five findings were retrieved and consecutively screened by at least 2 reviewers. This led to 88 original publications that were as feasible and should be applied according to the Earth-based guidelines of the AHA/ERC in relation to fundamental statements, like urgent recognition and action, focus on high-quality chest compressions, compression depth and compression-ventilation ratio. However, the special circumstances presented by microgravity and spaceflight must be considered concerning central points such as rescuer position and methods for the performance of chest compressions, airway management and defibrillation.

CPR in microgravity is feasible and should be applied according to the Earth-based guidelines of the AHA/ERC in relation to fundamental statements, like urgent recognition and action, focus on high-quality chest compressions, compression depth and compression-ventilation ratio. However, the special circumstances presented by microgravity and spaceflight must be considered concerning central points such as rescuer position and methods for the performance of chest compressions, airway management and defibrillation.

Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness. The two most prevalent forms of CMD, collagen VI-related myopathies (COL6RM) and laminin α2 deficient CMD type 1A (MDC1A), are both caused by deficiency or dysfunction of extracellular matrix proteins. Previously, we showed that an intramuscular transplantation of human adipose-derived stem cells (ADSC) into the muscle of the Col6a1

mice results in efficient stem cell engraftment, migration, long-term survival, and continuous production of the collagen VI protein, suggesting the feasibility of the systemic cellular therapy for COL6RM. In order for this therapeutic approach to work however, stem cells must be efficiently targeted to the entire body musculature. Thus, the main goal of this study is to test whether muscle homing of systemically transplanted ADSC can be enhanced by employing muscle-specific chemotactic signals originating from CMD-affected musely, identified molecules provided insight into the mechanisms governing directional migration and intramuscular trafficking of systemically infused stem cells, thus, permitting broad and effective application of the therapeutic adult stem cells for CMD treatment.

Collectively, identified molecules provided insight into the mechanisms governing directional migration and intramuscular trafficking of systemically infused stem cells, thus, permitting broad and effective application of the therapeutic adult stem cells for CMD treatment.

Mesenchymal stem cells (MSCs) activate the endogenous immune regulatory system, inducing a therapeutic effect in recipients. MSCs have demonstrated the ability to modulate the differentiation of myeloid cells toward a phagocytic and anti-inflammatory profile. Allogeneic, adipose-derived MSCs (ASCs) have been investigated for the management of complex perianal fistula, with darvadstrocel being the first ASC therapy approved in Europe in March 2018. Additionally, ASCs are being explored as a potential treatment in other indications. Yet, despite these clinical advances, their mechanism of action is only partially understood.

Freshly isolated human monocytes from the peripheral blood were differentiated in vitro toward M0 non-polarized macrophages (Mphs), M1 pro-inflammatory Mphs, M2 anti-inflammatory Mphs, or mature dendritic cells (mDCs) in the presence or absence of ASCs, in non-contact conditions. The phenotype and function of the differentiated myeloid populations were determined by flow cytometry, and mical inhibition of PGE2 with indomethacin abolished this modulatory effect, whereas treatment with a neutralizing anti-IL-6 antibody resulted in a partial abolishment. The knock-down of COX-2 in ASCs and the use of IL-1β-activated ASC-conditioned media confirmed the key role of PGE2 in ASC-mediated myeloid modulation. In our in vitro experimental settings, ASCs failed to modulate the phenotype and function of terminally polarized M1 Mphs.

The results demonstrate that ASCs are able to modulate the in vitro differentiation of myeloid cells toward an anti-inflammatory and reparative profile. This modulatory effect was mediated mainly by PGE2 and, to a lesser extent, IL-6.

The results demonstrate that ASCs are able to modulate the in vitro differentiation of myeloid cells toward an anti-inflammatory and reparative profile. This modulatory effect was mediated mainly by PGE2 and, to a lesser extent, IL-6.