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- Pennell, C. E., et al.
(författare)
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Genetic epidemiologic studies of preterm birth: guidelines for research
- 2007
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Ingår i: Am J Obstet Gynecol. - 1097-6868. ; 196:2, s. 107-18
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Tidskriftsartikel (refereegranskat)abstract
- Over the last decade, it has become increasingly apparent that the cause of preterm birth is multifactorial, involving both genetic and environmental factors. With the development of new technologies capable of probing the genome, exciting possibilities now present themselves to gain new insight into the mechanisms leading to preterm birth. This review aims to develop research guidelines for the conduct of genetic epidemiology studies of preterm birth with the expectation that this will ultimately facilitate the comparison of data sets between study cohorts, both nationally and internationally. Specifically, the 4 areas addressed in this review includes: (1) phenotypic criteria, (2) study design, (3) considerations in the selection of control populations, and (4) candidate gene selection. This article is the product of discussions initiated by the authors at the 3rd International Workshop on Biomarkers and Preterm Birth held at the University of California, Los Angeles, Los Angeles, CA, in March 2005.
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- Krishna Vadivel, Chella, et al.
(författare)
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Staphylococcus aureus induce drug resistance in cancer T cells in Sézary Syndrome
- 2024
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 143:15, s. 1496-1512
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Tidskriftsartikel (refereegranskat)abstract
- Key Points Enterotoxins from Staphylococcus aureus bacteria induce drug resistance in primary malignant T cells in Sézary syndrome. Targeting bacteria, their toxins, and downstream signaling pathways in malignant T cells abrogate the induction of drug resistance. Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T cell lymphoma (CTCL), are prone to Staphylococcus aureus (S. aureus) infections and have a poor prognosis due to treatment-resistance. Here, we report that S. aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T-cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S. aureus and recombinant SE significantly inhibit cell death induced by HDAC inhibitor romidepsin in primary malignant T-cells from SS patients. Bacterial killing by engineered, bacteriophage-derived, S. aureus-specific endolysin (XZ.700) abrogates the effect of S. aureus supernatant. Likewise, mutations in MHC Class II binding sites of SE type-A (SEA) and anti-SEA antibody block induction of resistance. Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide). Multimodal single-cell sequencing indicates TCR, NFB, and JAK/STAT signaling pathways (previously associated with drug-resistance) as putative mediators of SE-induced drug resistance. In support, inhibition of TCR-signaling and Protein Kinase C (upstream of NFB) counteracts SE-induced rescue from drug-induced cell death. Inversely, SE cannot rescue from cell death induced by proteasome/NFB inhibitor bortezomib. Inhibition of JAK/STAT only blocks SE-induced rescue of malignant T-cells in some but not all patients, suggesting two distinct ways SE can induce drug resistance. In conclusion, we show that S. aureus enterotoxins induce drug-resistance in primary malignant T-cells. These findings suggest that S. aureus enterotoxins cause clinical treatment-resistance in SS patients and that anti-bacterial measures may improve the outcome of cancer-directed therapy in patients harboring S. aureus
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