Laboratory of Experimental Anticancer Therapy

Research topics: tumor metastases, tumor angiogenesis, experimental anticancer therapy, immunotherapy of tumors, preclinical studies of new potential anticancer drugs. Research tasks:

  • The influence of vitamin D and its derivatives on the tumor microenvironment in the young and old organism.
  • Research on the mechanisms of vitamin D interaction with anticancer drugs in colon cancer, lung cancer and breast cancer.
  • New isothiocyanate derivatives and new bisphosphonates for use in anti-cancer therapy.
  • Immunotherapy in colon cancer using genetically modified dendritic cells as components of a combined immunomodulating therapy in the cancer microenvironment.
  • MicroRNA in cancer; including the involvement of microRNA in the process of invasive growth of breast cancer and in the mechanism of vitamin D action in breast cancer.
Laboratory Head

Head: prof. dr hab. Joanna Wietrzyk (0000-0003-4980-6606)

EDUCATION

1990–1996: Faculty of Veterinary Medicine, Agricultural Academy in Wroclaw, Poland
1996: the professional title of veterinarian (DVM)
2001 (28.06): doctor in biological sciences in the field of biology (PhD), specialization: cancers biology
2010 (25.02): habilitated doctor in biological sciences in the field of biology, specialization: experimental oncology
2018 (09.05): professor in biological sciences

Scientific activity:

  • ~ 231 published original works, 12 reviews, ~ 300 congress communications, 50 patent applications or patents.
  • Supervised 12 doctoral theses (including 2 interdisciplinary) and ~ 50 master’s theses, 2 open doctoral theses; reviewer of 13 doctorates and 1 habilitation, member of 4 habilitation committees.
  • The sum of the citations of all publications by Web of Science is 2888 (without self-citations); the index h is 31.
  • Member of the EACR (European Association for Cancer Research).
  • Member of PTIDiK (Polish Society of Experimental and Clinical Immunology).
  • Member from 2006, and from 2010 – January 2014 and from 2016 – currently; Chair of the Local Ethics Committee for Experiments on Animals in Wroclaw, Poland
Team

Assistant Professors:

PhD Students:

Most important scientific achievements
  • Development of experimental therapeutic strategies using vitamin D analogues (PRI-2191 and PRI-2205) and known anticancer drugs:
    a) 5-fluorouracil (5-FU; also irinotecan and oxaliplatin) in colon cancer models
    b) Imatinib and sunitinib in a non-small cell lung cancer model
  • Development of therapeutic strategies for inhibition of the metastasis process by interfering with the activity of platelets and vascular endothelial cells.
  • Demonstration that vitamin D and its derivatives by influencing the primary tumor microenvironment may intensify the process of mouse breast cancer metastasis.
Research methods
  • molecular biology
  • ELISA tests, flow cytometry
  • fluorescence microscopy
  • automated western blot with the possibility of multiplexing
  • orthotopic tumor cell transplants (including xenografts) (bladder, intestine, prostate, etc.)
Key equipment
  • Biotek Synergy H4 multi-functional plate reader with an automatic plate feeder; enables the reading of biological tests with detection based on absorbance, fluorescence, luminescence and fluorescence polarization.
  • BD LSRFortessa flow cytometer with an attachment for high-throughput analyzes; enables the simultaneous analysis of 18 labeled markers in cells.
  • NanoDrop 2000 UV-Vis Thermo Fisher Scientific spectrophotometer for concentration determination and evaluation of RNA and DNA purity in samples for PCR analyzes.
  • Olympus IX81 fluorescence microscope with the possibility of registering images in visible light, phase contrast and three fluorescent channels simultaneously; the device is adapted to work with microscope slides and multi-well plates.
  • RealTime-PCR instrument Viia7 Life Technologies with small laboratory equipment necessary for PCR analyzes.
  • The apparatus for in vivo ultrasound analyzes VisualSonics Vevo2100 with the necessary equipment (including an anesthesia station).
  • Carestream Image Station 4000MM PRO with an X-ray attachment for visualization of fluorescence, luminescence and RT in a living organism.
  • JESS device for automatic western-blot analyzes.
Most important projects (during the last 10 years)
  • The role of osteopontin in the effect of calcitriol and tacalcitol on the differentiation of Th17 cells in young and old mice with mammary gland cancer. NCN, OPUS 18, 02.10.2020-01.10.2024, prof. dr hab. Joanna Wietrzyk.
  • Synthesis and biofunctionalization of nanoparticles with high boron content; use in targeted boron-neutron therapy. NCN, OPUS-17, 2020-02-18- 2023-02-17 Elżbieta Pajtasz-Piasecka kierownik grantu. Projekt realizowany  jako konsorcjum IITD i AGH
  • Effect of SIRT1 deacetylase and epigenetic changes on the biological activity of vitamin D against lung cancer cells. NCN, SONATA, 02.09.2019 – 01.09.2022, dr Ewa Maj.
  • Effect of vitamin D on macrophages and fibroblasts accompanying breast cancer. NCN, OPUS 14, 26.09.2018-25.09.2021, prof. dr hab. Joanna Wietrzyk. W konsorcjum: IITD – lider, partnerzy: Dolnośląskie Centrum Onkologii i Uniwersytet Medyczny we Wrocławiu
  • Mercapturic acids – derivatives of natural isothiocyanates and modulators of tubulin polymerization in the combined therapy of bladder cancer. NCN, SONATA 13, 2018-05-07 – 2021-05-06, dr inż. Mateusz Psurski.
  • Effect of microvesicles released by dendritic cells of myeloid origin cultured in the presence of vitamin D analogues on leukemic cells. NCN, MINIATURA 2, 18.09.2018-17.09.2019, dr Eliza Turlej.
  • Genetically modified dendritic cells as a component of combined therapy immunomodulating the neoplastic microenvironment. NCN, OPUS 14, 31-07-2018 – 30-07- 2021, dr hab. Elżbieta Pajtasz-Piasecka.
  • The role of vitamin D in the effect of macrophages on neoplastic cells in a mouse mammary carcinoma model. NCN, PRELUDIUM 13, 06.02.2018-05.02.2021, dr Artur Anisiewicz.
  • The role of miRNA in the differentiation of human leukemia and lymphoma cells under the influence of calcitriol and its analogue PRI-2191. NCN, PRELUDIUM 9, 24.02.2016 – 23.02.2019, dr Justyna Trynda.
  • Investigation of the biological activity of selected aminomethylidene bisphosphonic acids. NCN, OPUS 7, 11.02.2015-10.02.2019, dr Anna Nasulewicz-Goldeman.
  • Pharmacotherapy of vascular endothelium and platelet activation dependent on prostacyclin, nitric oxide and carbon monoxide – a new strategy in the prevention of cancer metastasis (METENDOPHA). NCBIR, STRATEGMED 1, 01.07.2015-30.10.2020, prof. dr hab. Joanna Wietrzyk, tasks 1 i 7 leader (IIET). Consortium leader: Jagiellonian University, Partners: Medical University of Łódź, Medical University of Gdańsk, Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wrocław, Medical University of Białystok, Latvian Institute of Organic Synthesis in Riga.
  • New compounds with anti-cancer activity that disrupt telomere functions (TARGETTELO). NCBIR, STRATEGMED 3, prof. dr hab. Joanna Wietrzyk, task 7 leader (IITD). Consortium leader: Gdańsk University of Technology, Consortium partners: University of Gdańsk, Medical University of Gdańsk, Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wrocław, Nencki Institute of Experimental Biology in Warsaw, Szpitale Wojewódzkie in Gdynia Sp. z o.o., Innovabion Sp. z o.o., EU-CONSULT Sp. z o.o.
  • Assessment of the anti-tumor activity of chemoimmunotherapy with methotrexate nanoconjugates and vaccines based on dendritic cells with silent expression of the IL-10 receptor. NCN, PRELUDIUM, 06.2016 – 06. 2020, mgr Agnieszka Szczygieł.
  • Effect of the use of dendritic cells co-transduced with the lentiviral carrier of the IL-12 and IL-18 genes on the activation of the antitumor response in the MC38 mouse colon cancer model. NCN, PRELUDIUM, 01.2016 – 01.2019, mgr inż. Jagoda Mierzejewska.
  • Cancer nanomedicine – from the bench to the bedside. Horizon 2020 Framework Programme of the EU: COST Action CA17140, 28.09.2018-27.09.2022, MC Member representing Poland: Prof. Joanna Wietrzyk. Grant Holder Institution: university of Lodz, MC Chair: Prof. Barbara Klajnert-Maculewicz.
  • Control of the inflammatory process related to the progression of breast cancer by vitamin D and its analogues. NCN, OPUS 6, 05.08.2014-04.08.2017, prof. dr hab. Joanna Wietrzyk. International grant with Centre de Recherche en Nutrition Humaine d’Auvergne, Unite´Maladies Metaboliques et Micronutriments, INRA, Centre de Recherche de Theix, 63122 St Gene`s Champanelle, France
  • Mechanism regulating the interaction of vitamin D analogue in combination with cytostatics and tyrosine kinase inhibitors in non-small cell lung cancer model. NCN, PRELUDIUM, 2014-2017, dr Ewa Maj.
  • Vascular endothelium in civilization diseases: from cognitive research to the offer of an innovative drug with endothelial activity. The task: Studies of the therapeutic efficacy of compounds with endothelial activity in the models of tumor metastasis. NCBIR, POIG, 01.03.2009-30.06.2015, dr hab. Joanna Wietrzyk, task leader.
  • Gram-negative bacteria lysis products as potential antineoplastic preparations. Chemical and biochemical characterization and study of biological activities. Development of an active substance production technology. Task: To study the antitumor and antimetastatic activity and the influence of the obtained preparations on the immune system. Development projectNr NR13-0089-06, 01.2010 – 31.12.2012, prof. dr hab. Joanna Wietrzyk, task leader.
  • Establishment of the Integrated NeoLek Laboratory – Experimental Oncology and Innovative Technologies implemented under the POIG, 2007-2013, Priority 2. R&D infrastructure, 2.1 Development of centers with high research potential, 2009-2011, including the Laboratory of Biomedical Chemistry (head Prof. Janusz Boratyński) and the Laboratory of Experimental Anticancer Therapy and the IITD Animal House (head: Dr. Joanna Wietrzyk).
  • Investigation of the role of the Erk1/2 signaling pathway protein in inhibiting cell proliferation in a model of human breast cancer under the influence of vitamin D and its analogue PRI-2191. MNiSW, 15.09.2009 do15.09.2012, dr Dagmara Kłopotowska.
  • Supporting antitumor therapy of colon cancer by using new vitamin D analogues. MNiSW, 2008-09-04 -2011-09-03, dr. Joanna Wietrzyk.
  • Design, synthesis and in vitro and in vivo studies of the antitumor potential of phosphono and phosphine analogues of sulforaphane and their mercapturic derivatives with the potential ability to inhibit histone deacylase. NCN, OPUS, 05.09.2012-04.09.2016, Consortium leader: dr hab. inż. Tadeusz Marek Gajda, Faculty of Chemistry, Lodz University of Technology, Contractors: Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wroclaw, Faculty of Chemistry, Wroclaw University of Technology, Faculty of Chemistry, University of Lodz. Joanna Wietrzyk: main contractor at IITD.
  • Study of the mechanism of antitumor action of vitamin D analogues in combination with anastrozole in a human breast cancer model. NCN, PRELUDIUM 4, 2013-2017, Beata Filip.
  • Investigation of the mechanisms of enhancing the anti-tumor activity of 5-fluorouracil by the use of vitamin D analogues in a colon cancer model. NCN, PRELUDIUM 4, 2013-2016, Magdalena Milczarek.
Selected publications
  • Diana Papiernik, Anna Urbaniak, Dagmara Kłopotowska, Anna Nasulewicz-Goldeman, Marcin Ekiert, Marcin Nowak, Joanna Jarosz, Monika Cuprych, Aleksandra Strzykalska, Maciej Ugorski, Rafał Matkowski, Joanna Wietrzyk. Retinol-binding protein 4 accelerates metastatic spread and increases impairment of blood flow in mouse mammary gland tumors. Cancers, 2020, 12 (3): 623.; https://pubmed.ncbi.nlm.nih.gov/32156052/
  • Artur Anisiewicz, Agata Pawlik, Beata Filip-Psurska, Joanna Wietrzyk. Differential impact of calcitriol and its analogs on tumor stroma in young and aged ovariectomized mice bearing 4T1 mammary gland cancer. Int. J. Mol. Sci. 2020, 21(17), 6359; https://pubmed.ncbi.nlm.nih.gov/32887237/
  • Agata Pawlik, Artur Anisiewicz, Beata Filip-Psurska, Dagmara Klopotowska, Magdalena Maciejewska, Andrzej Mazur, Joanna Wietrzyk. Divergent effect of tacalcitol (PRI-2191) on Th17 cells in 4T1 tumor bearing young and old ovariectomized mice. Aging and Disease, 2020, 11 (2): 241-253.; https://pubmed.ncbi.nlm.nih.gov/32257539/
  • Kseniia Porshneva, Diana Papiernik, Mateusz Psurski, Agnieszka Łupicka-Słowik, Rafał Matkowski, Marcin Ekiert, Marcin Nowak, Joanna Jarosz, Joanna Banach, Magdalena Milczarek, Tomasz M. Goszczyński, Marcin Sieńczyk, Joanna Wietrzyk. Temporal inhibition of mouse mammary gland cancer metastasis by CORM-A1 and DETA/NO combination therapy. Theranostics, 2019; 9(13): 3918-3939.; https://pubmed.ncbi.nlm.nih.gov/31281522/
  • Magdalena Milczarek, Joanna Rossowska, Dagmara Klopotowska, Martyna Stachowicz, Andrzej Kutner, Joanna Wietrzyk. Tacalcitol increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating the thymidylate synthase. Journal of Steroid Biochemistry and Molecular Biology, 2019, 190: 139-151.; https://pubmed.ncbi.nlm.nih.gov/30923017/
  • Ewa Maj, Justyna Trynda, Beata Maj, Katarzyna Gębura, Katarzyna Bogunia-Kubik, Michał Chodyński, Andrzej Kutner, Joanna Wietrzyk. Differential response of lung cancer cell lines to vitamin D derivatives depending on EGFR, KRAS, p53 mutation status and VDR polymorphism. J. Steroid Biochem. Mol. Biol. 2019, 193:105431. https://pubmed.ncbi.nlm.nih.gov/31326626/
  • Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka. Reprogramming the murine colon cancer microenvironment using lentivectors encoding shRNA against IL-10 as a component of a potent DC-based chemoimmunotherapy. J Exp Clin Cancer Res. 2018 t. 37:126; https://pubmed.ncbi.nlm.nih.gov/29954431/
  • Artur Anisiewicz, Agata Pawlik, Beata Filip-Psurska, Eliza Turlej, Stanisław Dzimira, Magdalena Milczarek, Katarzyna Gdesz, Diana Papiernik, Joanna Jarosz, Dagmara Kłopotowska, Andrzej Kutner, Andrzej Mazur, Joanna Wietrzyk. Unfavorable effect of calcitriol and its low-calcemic analogs on metastasis of 4T1 mouse mammary gland cancer. Int J Oncology 2018, 52(1): 103-126; https://pubmed.ncbi.nlm.nih.gov/29115583/
  • Mateusz Psurski, Łukasz Janczewski, Marta Świtalska, Anna Gajda, Tomasz M. Goszczyński, Józef Oleksyszyn, Joanna Wietrzyk, Tadeusz Gajda. Novel phosphonate analogs of sulforaphane: synthesis, in vitro and in vivo anticancer activity. Eur J Med Chem, 2017, 132: 63-80.; https://pubmed.ncbi.nlm.nih.gov/28342398/
  • Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka. Intratumoral Lentivector-Mediated TGF-β1 Gene Downregulation As a Potent Strategy for Enhancing the Antitumor Effect of Therapy Composed of Cyclophosphamide and Dendritic Cells. Front Immunol. 2017, 8: 713. doi: 10.3389/fimmu.2017.00713. eCollection 2017.; https://pubmed.ncbi.nlm.nih.gov/28713366/