Małgorzata Bajor - Academia.edu (original) (raw)

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Papers by Małgorzata Bajor

Breast Cancer Research, Jul 10, 2014

Cancer Research, May 1, 2015

Increasing evidence indicates that oxidative stress is involved in the progression of estrogen re... more Increasing evidence indicates that oxidative stress is involved in the progression of estrogen receptor (ER)-positive breast cancer. A moderate increase in cellular oxidants contributes to the genomic instability and to the change in cellular growth pattern, which in turn can facilitate progressive transformation of normal cells into cancer cells. Accordingly, the oxidative stress-related gene expression signature has been suggested to correlate with therapy resistance and poorer outcome in breast cancer. Therefore, it is crucial to determine the antioxidant defense mechanisms that are utilized by breast cancer cells to regulate oxidative stress. Peroxiredoxin 1 (PRDX1) is one of the most prevalent hydrogen peroxide scavenging enzymes in mammalian cells. Our recent studies indicated that PRDX1 is an independent biomarker of favorable prognosis in ER-positive breast cancer. Our results indicate the mechanistic link between PRDX1 and ERα in breast cancer and suggest a role for PRDX1 in mammary carcinogenesis. We provide a molecular explanation for this phenomenon in the current project. To evaluate the importance of PRDX1 activity in ER-positive breast cancer, we have used adenanthin, a newly described PRDX1/2 inhibitor. In our studies, we have shown that adenanthin strongly inhibits metabolism of exogenous hydrogen peroxide by breast cancer cells. This phenomenon is accompanied by a shift from H2O2-degrading PRDX1 dimers into enzymatically inactive monomers and by a dramatic decrease of ERα protein presence in the cells. Moreover, we have observed that incubation of ER-positive breast cancer cells with adenanthin leads to a marked increase in phosphorylation status of proteins associated with Src-Akt-driven signaling in breast cancer. Thus, our results suggest that PRDX1 can play an important role in controlling the switch between estrogen receptor- and growth factor-driven signaling in breast cancer. In summary, in our studies we describe for the first time molecular consequences of rapid dysfunction of PRDX-related system in ER-positive breast cancer. The deeper knowledge on the mechanisms of PRDX1 functioning can change our understanding of the events leading to the progression of ER-positive breast cancer and provide new opportunities for pharmacological interventions in this disease, especially in the context of recent observations connecting the oxidative stress and resistance to endocrine therapy. Citation Format: Malgorzata Bajor, Agata O Zych, Patrick C O'Leary, Anna Czekalska, William M Gallagher, Jakub Golab, Radoslaw Zagozdzon. Adenanthin, a new peroxiredoxin inhibitor, induces a switch between estrogen receptor alpha-mediated and Src/Akt-driven signaling in breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-07-09.

Cancer Letters, Feb 1, 2020

Archivum Immunologiae Et Therapiae Experimentalis, Jan 17, 2018

Haematologica, Jul 12, 2018

Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for c... more Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles. Kinetics experiments revealed that CAR expression was optimal after 3 days of IL15 stimulation prior to transfection, consistently achieving over 80% expression. CAR-engineered NK cells acquired increased degranulation toward CD19+ targets, and maintained their intrinsic degranulation response toward CD19− K562 cells. The response of redirected NK-cell subsets against CD19+ targets was dependent on their intri...

Supplementary Video 1. Time-lapse sequence of a serial killer NK cell attacking a cluster of six ... more Supplementary Video 1. Time-lapse sequence of a serial killer NK cell attacking a cluster of six 221 cells in a 50Ã-50Ã-300 Î¼m3 microwell. The movie plays the same sequence simultaneously side-by-side in fluorescence (left) and bright field (right). The NK cell is shown in blue (in both panels), live targets are shown in green and dead targets in red. At the end of the movie five target cells have been killed. Total imaging time was 4.5 hours with 10 minutes between frames.

Blood, 2014

Peroxiredoxins (PRDXs) are abundant antioxidant enzymes. In mammals there are six PRDXs. Among th... more Peroxiredoxins (PRDXs) are abundant antioxidant enzymes. In mammals there are six PRDXs. Among them, four (PRDXs 1-4) are functional dimers. PRDXs are oxidoreductases that scavenge peroxides with reducing equivalents from thioredoxin-thioredoxin reductase system. PRDXs function as a defense against redox stress but their role far exceeds peroxides removal. They directly support the activation of several protein tyrosine phosphatases thus suppressing kinase-mediated signaling. PRDXs are usually highly expressed in tumor cells, but there are cases of their epigenetic downregulation. Depending on a particular experimental model and the stage of tumor development, PRDXs can either suppress or support tumor cell growth. The role of peroxiredoxins in B-cell derived tumors has not been studied so far. We have used two Burkitt's lymphoma cell lines: Raji and Ramos. To isolate protein targets for a novel small molecule peptidomimetic inhibitor (Klossowski, 2012, J Med Chem) with antitumo...

British Journal of Cancer, 2018

(A) Integrated heat plots for holo Ca2+-S100BS... more (A) Integrated heat plots for holo Ca2+-S100BSH and holo Ca2+-S100BSNO protein with ZnSO4 in 10 mM TES buffer, pH 7.2, 15 mM NaCl. (B) Integrated heat plots for apo S100BSH and apo S100BSNO protein with ZnSO4 in 10 mM TES buffer, pH 7.2, 15 mM NaCl. (C) Integrated heat plots for apo S100BSH and apo S100BSNO protein with ZnSO4 in 10 mM TES buffer, pH 7.2, 150 mM NaCl.</p

ITC-derived thermodynamic parameters for Zn2+ binding to S100BSH ... more ITC-derived thermodynamic parameters for Zn2+ binding to S100BSH and S100BSNO protein dimer.</p

ITC-derived thermodynamic parameters for Ca2+ binding to S100BSH ... more ITC-derived thermodynamic parameters for Ca2+ binding to S100BSH and S100BSNO protein monomers.</p

Experiments were performed at (A) 10 mM TES buffer, pH 7.2, 10 mM CaCl2</s... more Experiments were performed at (A) 10 mM TES buffer, pH 7.2, 10 mM CaCl2, 15 mM NaCl; (B) 10 mM TES buffer, pH 7.2, 15 mM NaCl and (C) 10 mM TES buffer, pH 7.2, 150 mM NaCl.</p

H/D exchange results for S100BSH and S100BSNO as assessed by liquid chromatography combi... more H/D exchange results for S100BSH and S100BSNO as assessed by liquid chromatography combined with mass spectrometry (LC-MS).</p