| 1. |
- Krishna Vadivel, Chella, et al.
(författare)
-
Staphylococcus aureus induce drug resistance in cancer T cells in Sézary Syndrome
- 2024
-
Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 143:15, s. 1496-1512
-
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
|
|
| 2. |
|
|
| 3. |
- Osmancevic, Amra, 1968, et al.
(författare)
-
A retrospective study on diagnostics and treatment outcomes of primary cutaneous B-cell lymphomas
- 2021
-
Ingår i: European Journal of Cancer, Abstracts, Supplement Volume 156S1, October 2021 ISSN 0959-8049, Page 71. - 0959-8049.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- EORTC Cutaneous Lymphoma Group 20-21 meeting abstract book | European Journal of Cancer 156S1 (2021) S1–S71 S 71: Epi-P-08 A retrospective study on diagnostics and treatment outcomes of primary cutaneous B-cell lymphomas Amra Osmancevic1,2, Karolina Wojewoda1,2 1 Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 2 Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Wojewoda, Karolina, et al.
(författare)
-
Diagnostic Outcomes and Treatment Modalities in Patients with Mycosis Fungoides in West Sweden-A Retrospective Register-Based Study
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:19
-
Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. The aim of this study was to describe the clinical features and epidemiological and diagnostic findings in addition to the treatment modalities and responses in patients with MF. Furthermore, comparisons between patients in the early stage and the advanced stage were evaluated. (2) Methods: A retrospective register-based study based on data collected from the primary cutaneous lymphoma register and medical records was performed at the Department of Dermatology and Venerology at Sahlgrenska University Hospital, Gothenburg, Sweden. (3) Results: Eighty-four patients with a median age of 55 years with MF were included. Most of the patients (n = 73) were diagnosed at the early stage of the disease (IA-IIA). Overall disease progression was seen in 12.5% (n = 9) of the patients. Nine (10.7%) patients were deceased, out of which four (4.8%) deaths were associated with MF-related causes. (4) Conclusions: This study contributes to the knowledge of the epidemiological and clinical features in addition to the diagnostic findings and treatment responses in patients with MF in Sweden.
|
|
| 7. |
- Wojewoda, Karolina, et al.
(författare)
-
Diagnostics and treatment of mycosis fungoides and Sézary syndrome in West Sweden: a retrospective register-based study of 82 patients
- 2021
-
Ingår i: European Journal of Cancer, Supplement Volume 156S1, October 2021 ISSN 0959-8049, Page 67. - 0959-8049.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- EORTC Cutaneous Lymphoma Group 20-21 meeting abstract book | European Journal of Cancer 156S1 (2021) S1–S71 S 67: Epi-P-01 Diagnostics and treatment of mycosis fungoides and Sézary syndrome in West Sweden: a retrospective register-based study of 82 patients Karolina Wojewoda1,2, Amra Osmancevic1,2 1 Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden 2 Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
|
|
| 8. |
- Wojewoda, Karolina, et al.
(författare)
-
Optimizing treatment of acne with photodynamic therapy (PDT) to achieve long-term remission and reduce side effects. A prospective randomized controlled trial.
- 2021
-
Ingår i: Journal of photochemistry and photobiology. B, Biology. - : Elsevier BV. - 1873-2682 .- 1011-1344. ; 223
-
Tidskriftsartikel (refereegranskat)abstract
- Photodynamic therapy with methyl aminolevulinate (MAL-PDT) is an effective treatment of acne vulgaris, but is associated with side effects. We performed a prospective randomized split-face study aimed at optimizing MAL-PDT treatment. Patients (n=33) were randomized to two or four treatments of PDT with MAL on one cheek and placebo vehicle on the other cheek, 1-2weeks apart. A 1.5-h pre-treatment with the MAL cream was followed by illumination with red light (20J/cm2). Assessments were performed before treatment and 4, 10, and 20weeks after the last treatment. In comparison to baseline, the number of inflammatory lesions at 20weeks on cheeks treated with MAL-PDT showed a relative decrease of 74% in the group with two treatments and 85% in the group with four treatments. This new treatment regimen for both MAL-PDT and red-light-only PDT, with shortened pre-treatment and reduced light dose, could be an effective modality.
|
|
