Prevalence of ongoing or previous SARS-CoV-2 infection among dental personnel - the Swedish experience.

Conclusions: The seroprevalence of SARS-CoV-2 infection was approximately similar to that in healthcare personnel, and approximately equal compared to that in the general population.

Materials And Methods: We carried out an observational cohort study from March to June 2020, including 341 employees randomly selected from Public Dental Service in the County of Stockholm. The primary outcome variable was the prevalence of SARS-CoV-2 RNA and/or antibodies against SARS-CoV-2.

Novel specific human and mouse stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) antibodies for biochemical and immunohistochemical analyses.

Matrix metalloproteinases (MMP) are a family of more than 25 zinc-dependent enzymes that are centrally involved in cellular migration, tissue remodeling, cancer invasion and metastasis. Besides degrading extracellular matrix proteins, MMPs are crucial for growth factor and cytokine release and activation. At the same time, they can inactivate inflammatory mediators and enzymes themselves through protein degradation.

Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.

Background: Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment.

Methods: We obtained acute myeloid leukaemia blast cells from unselected patients attending our UK hospital between Feb 19, 2010, and Jan 20, 2014.

Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma.

Multiple Myeloma (MM) is a haematologic malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. Over the last 10-15 y the introduction of the proteasome-inhibitor bortezomib has improved MM prognosis, however relapse due to bortezomib-resistance is inevitable and the disease, at present, remains incurable. To model bortezomib-resistant MM we generated bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma cells from patients relapsing after bortezomib treatment (n = 6 ).

Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML.

Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies. Recently we reported that ibrutinib inhibits human acute myeloid leukemia (AML) blast proliferation and leukemic cell adhesion to the surrounding bone marrow stroma cells. Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo.

Overcoming bortezomib resistance in multiple myeloma.

The introduction of the proteasome inhibitor bortezomib in 2003 significantly improved treatment of the B-cell malignancy MM (multiple myeloma). Relapse following bortezomib therapy is inevitable, however, and MM remains an incurable disease. In the present mini-review, we explore the mechanisms by which bortezomib resistance occurs in MM, including inherent and acquired mutation, and inducible pro-survival signalling.

Identification of Bruton's tyrosine kinase as a therapeutic target in acute myeloid leukemia.

Bruton's tyrosine kinase (BTK) is a cytoplasmic protein found in all hematopoietic cell lineages except for T cells. BTK mediates signaling downstream of a number of receptors. Pharmacologic targeting of BTK using ibrutinib (previously PCI-32765) has recently shown encouraging clinical activity in a range of lymphoid malignancies.

Understanding the role of NRF2-regulated miRNAs in human malignancies.

Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a key transcription factor that regulates the expression of over a hundred cytoprotective and antioxidant genes that provide cellular protection from reactive oxygen species. Chemotherapy resistance in several cancers has been linked to dysregulation of the NRF2 signalling pathway, moreover there is growing evidence that NRF2 may contribute to tumorigenesis. MicroRNA (miRNA) are small non-coding RNA sequences that post-transcriptionally regulate mRNA sequences.

Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression.

Dexamethasone is a key front-line chemotherapeutic for B-cell malignant multiple myeloma (MM). Dexamethasone modulates MM cell survival signaling but fails to induce marked cytotoxicity when used as a monotherapy. We demonstrate here the mechanism behind this insufficient responsiveness of MM cells toward dexamethasone, revealing in MM a dramatic anti-apoptotic role for microRNA (miRNA)-125b in the insensitivity toward dexamethasone-induced apoptosis.

Macrophage migration and invasion is regulated by MMP10 expression.

This study was designed to identify metalloproteinase determinants of macrophage migration and led to the specific hypothesis that matrix metalloproteinase 10 (MMP10/stromelysin-2) facilitates macrophage migration. We first profiled expression of all MMPs in LPS-stimulated primary murine bone marrow-derived macrophages and Raw264.7 cells and found that MMP10 was stimulated early (3 h) and down-regulated later (24 h).

The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance.

NF-E2-related factor 2 (Nrf2) transcription factor regulates a range of cytoprotective transcriptional responses, preventing further cellular injury by removing biochemical damage and renewing tissue. Here we show that acute myeloid leukemia (AML) cells possess greater constitutive nuclear levels of Nrf2 than normal control CD34(+) cells because of an imbalance between mRNA expression levels of Nrf2 and its inhibitor Keap1 but not through their somatic mutation. Elevated Nrf2 was reduced by NF-κB inhibitors.

BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib and lenalidomide activities through NF-κB.

Ibrutinib (previously known as PCI-32765) has recently shown encouraging clinical activity in chronic lymphocytic leukaemia (CLL) effecting cell death through inhibition of Bruton's tyrosine kinase (BTK). In this study we report for the first time that ibrutinib is cytotoxic to malignant plasma cells from patients with multiple myeloma (MM) and furthermore that treatment with ibrutinib significantly augments the cytotoxic activity of bortezomib and lenalidomide chemotherapies. We describe that the cytotoxicity of ibrutinib in MM is mediated via an inhibitory effect on the nuclear factor-κB (NF-κB) pathway.

Understanding the role of miRNA in regulating NF-κB in blood cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary sequences in mRNAs encoding downstream target genes. A large variety of cellular processes, including differentiation, development, apoptosis and cell cycle progression, are dependent on miRNA-mediated suppression of gene expression for their regulation. As such, it is unsurprising that these small RNA molecules are associated with signaling networks that are often altered in various diseases, including many blood cancers.

Micro RNAs as a new therapeutic target towards leukaemia signalling.

Micro RNAs (miRNAs) have emerged as potentially useful and specific agents to regulate transcriptional control of many cellular genes. There is a real prospect that miRNA and other short-length RNA reagents could be useful in a therapeutic setting. Here we outline the control of miRNAs in acute myeloid leukaemia (AML) subtype of human leukaemia, and ask whether miRNA could be important either in the generation of an AML phenotype, or as a variety of agents to combat the disease in the clinic.