| 1. |
- Hombach-Klonisch, Sabine, et al.
(author)
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Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response
- 2018
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In: Pharmacology and Therapeutics. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0163-7258 .- 1879-016X. ; 184, s. 13-41
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Research review (peer-reviewed)abstract
- Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15 months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB.
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| 2. |
- Likus, Wirginia, et al.
(author)
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Bacterial Infections and Osteoclastogenesis Regulators in Men and Women with Cholesteatoma
- 2016
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In: Archivum Immunologiae et Therapiae Experimentalis. - : SPRINGER BASEL AG. - 0004-069X .- 1661-4917. ; 64:3, s. 241-247
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Research review (peer-reviewed)abstract
- One of the most distinct features of middle ear cholesteatoma is bone destruction. Aetiology of cholesteatoma is thought to be multifactorial. Endotoxins produced by bacteria are thought to initiate the inflammation process in the middle ear leading to cholesteatoma. There are physiological differences in bone metabolism between men and women. The aim of our study was the immunohistochemical evaluation of the contents of two key components of the OPG/RANK/RANKL triad-RANKL and OPG in cholesteatoma, to analyse if there are any differences between the sexes and to evaluate the bacteria species isolated from cholesteatoma just before surgical treatment and to evaluate their plausible influence on the expression of OPG and RANKL in cholesteatoma. Twenty-one adult patients with acquired cholesteatoma who underwent surgery were analysed. There were no statistically significant differences in the expression of both regulators of osteoclastogenesis between the sexes. In 38.1 % patients cholesteatoma was not infected, whereas in 61.9 % patients various bacterial infections or mycosis were found. The most frequently isolated species was Pseudomonas aeruginosa (14.29 % infections) followed by Staphylococcus aureus (9.52 % infections). There were no statistically significant differences in expression of both OPG and RANKL between uninfected and infected cholesteatomas.
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| 3. |
- Likus, Wirginia, et al.
(author)
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Could drugs inhibiting the mevalonate pathway also target cancer stem cells?
- 2016
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In: Drug resistance updates. - : CHURCHILL LIVINGSTONE. - 1368-7646 .- 1532-2084. ; 25, s. 13-25
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Research review (peer-reviewed)abstract
- Understanding the connection between metabolic pathways and cancer is very important for the development of new therapeutic approaches based on regulatory enzymes in pathways associated with tumorigenesis. The mevalonate cascade and its rate-liming enzyme HMG CoA-reductase has recently drawn the attention of cancer researchers because strong evidences arising mostly from epidemiologic studies, show that it could promote transformation. Hence, these studies pinpoint HMG CoA-reductase as a candidate proto-oncogene. Several recent epidemiological studies, in different populations, have proven that statins are beneficial for the treatment-outcome of various cancers, and may improve common cancer therapy strategies involving alkylating agents, and antimetabolites. Cancer stem cells/cancer initiating cells (CSC) are key to cancer progression and metastasis. Therefore, in the current review we address the different effects of statins on cancer stem cells. The mevalonate cascade is among the most pleiotropic, and highly interconnected signaling pathways. Through G-protein-coupled receptors (GRCP), it integrates extra-, and intracellular signals. The mevalonate pathway is implicated in cell sternness, cell proliferation, and organ size regulation through the Hippo pathway (e.g. Yap/Taz signaling axis). This pathway is a prime preventive target through the administration of statins for the prophylaxis of obesity related cardiovascular diseases. Its prominent role in regulation of cell growth and sternness also invokes its role in cancer development and progression. The mevalonate pathway affects cancer metastasis in several ways by: (i) affecting epithelial-to-mesenchymal transition (EMT), (ii) affecting remodeling of the cytoskeleton as well as cell motility, (iii) affecting cell polarity (non-canonical Wnt/planar pathway), and (iv) modulation of mesenchymal-to-epithelial transition (MET). Herein we provide an overview of the mevalonate signaling network. We then briefly highlight diverse functions of various elements of this mevalonate pathway. We further discuss in detail the role of elements of the mevalonate cascade in sternness, carcinogenesis, cancer progression, metastasis and maintenance of cancer stem cells. (C) 2016 The Authors. Published by Elsevier Ltd.
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| 4. |
- Mazurek, Klaudia, et al.
(author)
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Assessment of connective tissue metabolism in patients with head and neck malignancies treated with radiotherapy
- 2023
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In: Otolaryngologia Polska. - : Copernicus International. - 0030-6657. ; 77:5, s. 23-29
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Journal article (peer-reviewed)abstract
- Introduction: Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells. Aim: The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy. Material and methods: The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy. Results: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation. Conclusions: The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue. Copyright © 2023 Polish Society of Otorhinolaryngologists Head and Neck Surgeons.
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