Browsing by Author "Strumfs, Boriss"

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    An easy route to aziridine ketones and carbinols
    (2021-12-05) Strumfs, Boriss; Hermane, Jekaterina; Belyakov, Sergey; Sobolevs, Artjoms; Velikijs, Kirils; Uljanovs, Romans; Trapencieris, Peteris; Strumfa, Ilze; Department of Pathology; Faculty of Medicine
    N,N-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective to amide carbonyl at a low (−78◦C) temperature. These ketones, in reaction with organolithium reagents, give symmetrical and unsymmetrical aziridinyl carbinols. The usage of excess phenyllithium may serve as a special N-Boc-protecting group cleavage method for acid-sensitive substrates.
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    Immunohistochemical Profile of Parathyroid Tumours : A Comprehensive Review
    (2022-07) Uljanovs, Romans; Sinkarevs, Stanislavs; Strumfs, Boriss; Vidusa, Liga; Merkurjeva, Kristīne; Strumfa, Ilze; Department of Pathology
    Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic CDC73 mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or upregulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immunophenotype is not the final proof of malignancy but should prompt the search for the definitive criteria for carcinoma. Histogenetic studies can be necessary for differential diagnosis between thyroid vs. parathyroid origin of cervical or intrathyroidal mass; detection of parathyroid hormone (PTH), chromogranin A, TTF-1, calcitonin or CD56 can be helpful. Finally, immunohistochemistry is useful in pathogenetic studies due to its ability to highlight both the presence and the tissue location of certain proteins. The main markers and challenges (technological variations, heterogeneity) are discussed here in the light of the current WHO classification (2022) of parathyroid tumours.
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    Molecular profile of parathyroid tissues and tumours : a heterogeneous landscape
    (2021-10) Uljanovs, Romans; Strumfa, Ilze; Bahs, Guntis; Vidusa, Liga; Merkurjeva, Kristine; Franckevica, Ivanda; Strumfs, Boriss; Rīga Stradiņš University
    Advances in laboratory diagnostics and surgical treatment of primary hyperpara-thyroidism have ensured solid basis for research in parathyroid pathology in order to specify key molecules in pathogenesis and morphological diagnostics of difficult cases. The aim of this study was to assess the molecular landscape and its heterogeneity in primary parathyroid hyperplasia (PPH) and adenoma, compared to carcinoma and normal glands. In a retrospective analysis of 179 surgically removed parathyroid glands (102 adenomas; 27 PPH; 45 normal glands; 5 carci-nomas), expression of Ki-67, p21, p27, p53, cyclin D1, Bcl-2 protein, vimentin, cytokeratin (CK) 19, E-cadherin, CD56, CD44 and parafibromin was detected by immunohistochemistry, followed by computer-assisted assessment of mean values and heterogeneity measures. Descriptive statistics and Kruskal-Wallis test were applied. Significant differences were disclosed regarding the mean and highest fraction of Ki-67 (both p < 0.001), p21 (both p < 0.001), cyclin D1 (p = 0.002) and p27-expressing cells (p = 0.010). Proliferative lesions (PPH, adenoma and carcinoma) showed statistically significantly up-regulated CK19 (p = 0.012), decreased E-cadherin levels and distinctive patterns of vimentin. CD44, CD56 and p53 were almost absent from parathyroid tissues. All carcinomas lacked parafibromin contrasting with invariable positivity in adenomas. Remarkable heterogeneity of cell cycle markers and intermediate filaments must be accounted for in scientific studies and elaboration of diagnostic cut-offs.
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    Non-Aziridination Approaches to 3-Arylaziridine-2-carboxylic Acid Derivatives and 3-Aryl-(aziridin-2-yl)ketones
    (2022-06-01) Strumfs, Boriss; Veļikijs, Kirils; Uljanovs, Romans; Sinkarevs, Stanislavs; Strumfa, Ilze; Department of Pathology
    Highly functionalized aziridines, including compounds with aromatic moieties, are attractive substrates both in synthetic and medical areas of chemistry. There is a broad and interesting set of synthetic methods for reaching these compounds. Aziridination represents the most explored tool, but there are several other more specific, less well-known, but highly promising approaches. Therefore, the current review focuses on recently described or updated ways to obtain 3-arylated aziridines via different non-aziridination-based synthetic methods, reported mainly since 2000. The presented methods belong to two main directions of synthesis, namely, cyclization of open-chain substrates and rearrangement of other heterocycles. Cyclization of open-chain substrates includes the classic Gabriel-Cromwell type cyclization of halogenated substrates with amines, base-promoted cyclization of activated aminoalcohols (or its analogues), and the oxidative cyclization of β-dicarbonyls. Rearrangements of other heterocycles are presented as the Baldwin rearrangement of 4-isoxazolines, the cycloaddition of 1.3-dipoles or dienes to 2H-azirines, and the addition of C-and N-nucleophiles to the double bond of azirines.
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    Tumour Microenvironment : The General Principles of Pathogenesis and Implications in Diffuse Large B Cell Lymphoma
    (2024-06) Sinkarevs, Stanislavs; Strumfs, Boriss; Volkova, Svetlana; Strumfa, Ilze; Department of Pathology
    Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide, constituting around 30–40% of all cases. Almost 60% of patients develop relapse of refractory DLBCL. Among the reasons for the therapy failure, tumour microenvironment (TME) components could be involved, including tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs), cancer-associated fibroblasts (CAFs), and different subtypes of cytotoxic CD8+ cells and T regulatory cells, which show complex interactions with tumour cells. Understanding of the TME can provide new therapeutic options for patients with DLBCL and improve their prognosis and overall survival. This review provides essentials of the latest understanding of tumour microenvironment elements and discusses their role in tumour progression and immune suppression mechanisms which result in poor prognosis for patients with DLBCL. In addition, we point out important markers for the diagnostic purposes and highlight novel therapeutic targets.