Hiljadnikova-Bajro, Marija

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Hiljadnikova-Bajro, Marija

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INTEGRATIVE OMICS APPROACH IN BREAST CANCER MANAGEMENT
(https://lm4ms.gr/images/LM4MS_ABSTRACTS.pdf, 2022-10)
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Djokoski, F.
INTEGRATIVE OMICS APPROACH IN BREAST CANCER MANAGEMENT Marija Hiljadnikova-Bajro, Filip Djokoski Institute for Applied Biochemistry, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, Skopje, Republic of North Macedonia Introduction As the most frequent malignancy and a leading cause of cancer death among women worldwide, breast cancer (BC) remains a huge challenge for multidisciplinary approaches in advancement of the diagnostic and treatment strategies. Aim To evaluate and highlight the potential of integrative omics approach in BC management. Methodology Comprehensive literature survey. Results The advanced genomic methodologies like next-generation sequencing, complemented with the novel insights in transcriptomics, epigenomics, proteomics, metabolomics and microbiomics, have set the scene for large-scale research aimed at discovery and clinical application of novel, highly specific laboratory markers to enable early diagnosis, precise prognosis and classification, timely and personalized treatment, effective monitoring or design of a targeted pharmacotherapy. Apart from breast tissue, specimens like urine, tumor interstitial fluid, blood, serum or plasma, saliva and the nipple aspirate fluid are frequently used as sources of biomarkers in clinical research involving various ‘omics approaches. The set of laboratory markers currently implemented in clinical practice, including CA 15-3, CEA, ER-, PR-, HER2-expression, BRCA1and 2 mutations, is expected to be supplemented with novel promising markers like microRNA molecules (oncomiR and TS-miRNAs), circulating RNAs, circulating tumor DNA, circulating cell free DNA, CA27.29 molecules, but potential is also identified for EZH2, GP88, Cyclin-E, B-Myb, Twist, DMP1β, RB1, novelty discovered hub genes like CENPL, ISG20L2, LSM4, MRPL3, and a number of metabolites, amino acids and lipids. The available ‘omics databases like PRIDE, COSMIC, GENIE, TCGA, CPTAC, GXB, GEO, HUPO and TACCO; the molecular assays including OncotypeDx and MammaPrint; cancer metabolic biomarker database (CMBD); the Human OncoBiome Database; the AURORA program, the BC epigenomics track hub, have aided substantially the integration of results and their in silico analysis, data access to independent research groups enabling evaluation of previously detected or identification of novel markers with clinical relevance including: genes, proteins, metabolites, microbiota-constituents. Conclusion The novel ‘omics technologies have dramatically changed our understanding of the mechanisms underlying cancer. Their integrative application holds huge potential in characterization of BC heterogeneity in a therapeutically meaningful way as well as identification of potential biomarkers to be used as hallmarks of the disease or targets for personalized drug design.
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The Potential of Salivary Proteome in Laboratory Analysis of Sjogren's Syndrome
(2022)
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Simovska, A
Detection of pathological processes at an early stage can significantly affect the clinical course and outcome of the disease, and hence the choice of appropriate therapeutic intervention. In order to achieve this and avoid invasive sampling procedures like surgical biopsy and repeated phlebotomies which introduce additional stress and safety issues in patients, research is greatly focused on identifying alternative samples and novel biomarkers for advanced laboratory analysis. Since many oral but also systemic pathological processes are being reflected in the salivary composition, it is getting increasing attention as an alternative sample to blood, especially for some population groups like children, adolescents, geriatric or psychiatric patients, where blood sampling is often compromised by insufficient cooperation from the patients or individual factors related to the patiens’ health. Sjögren's syndrome (SS) is an autoimmune disease with an insidious onset, variable course and clinical presentation, so its diagnosis is usually established about 6 years after the initiation of the disease and based on the detection and quantification of circulating autoantibodies such as: anti-Ro/SSA, anti-La/SSB, anti-muscarinic receptor antibodies, anti-nuclear antibodies and rheumatoid factor. Apart from molecular diagnostics and nanotechnology, several new approaches emerge for detecting even subtle alterations of the salivary constituents, like proteins which are employed in the proteomic analysis. Numerous proteomic studies involving sophisticated methodology like LC-MS/MS have identified aberrant expression of specific proteins in saliva of SS patients, making them potential markers of the disease and indicators of progression. Beside cytokines, many other proteins involved in the inflammatory process are upregulated vs proteins associated with the salivary production which are downregulated. Further to changes in salivary concentrations of MMP9, Complement factor B, Azurocydin Kallikrein, many other proteins including proteases like Trypsin, Catepsin, and Myeloblastin, inhibitors of Cystein proteases, Calreticulin, Protein 29, α-amylase precursor of carbonanhydrase VI, β-2 microglobulin, enolase etc. have shown aberrant expression in saliva from SS patients and a recent study has even proposed the combination of serum anti-SSA/Ro and upregulated salivary TRIM29, as an optimal marker with high diagnostic accuracy for fast and noninvasive diagnosis of SS. But, in patients with SS, efficient saliva collection is difficult because saliva secretion is significantly reduced. Therefore, when examining
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The Emerging Power of miRNAs in Management of Acute Coronary Syndrome
(2023)
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Filip Djokoski
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Biomolecular laboratory markers in cancer management
(2017)
The laboratory analysis is a compulsory supplement to clinical evaluation in making decisions upon diagnosis and treatment of cancer, one of the leading causes of death worldwide. The traditional biochemical laboratory protocols employed in diagnosis, prognosis and monitoring of malignant diseases include testing of soluble macromolecules as tumor markers and certain common parameters corresponding to the specific type of malignancy, but their limited reliability urges the necessity of identifying new biomarkers with higher specificity, sensitivity and predictability. Biomolecular/genetic testing is an emerging field within the scope of laboratory analysis with high clinical potential based on the assumption that revealing the genetic profile unique to each individual cancer may help predict the prognosis and select an appropriate treatment to target the changes in the specific tumor. This work reviews the currently available genomic laboratory tests and highlights their clinical and scientific relevance. Implication of aberrant transcripts BCR-ABL and PML-RAR for the management of leukemias, detection of genetic and epigenetic aberrations associated with familial cancer syndromes (MMR gene defects in Lynch Syndrome), pharmacogenetic assays for HER2, EGFR, ALK, KRAS, BRAF, UGT1A1 testing for selection of appropriate most efficient and least toxic treatment of particular cancer types will be addressed, along with novel, recently identified markers with anticipated clinical impact. The rapid development of high throughput technologies shifting singleplex towards multiplex testing, such as the next generation sequencing paired with bioinformatics which enable fast and affordable sequencing of the entire genome of an individual, will inevitably empower accelerated establishment of new biomolecular markers associated with the process of cancer initiation and progression. A comparative overview of the contemporary methodologies will be presented in the lecture. Multidisciplinary efforts should be made to implement the benefits from the technological advancement in the scientific process of new biomarker identification and translation of the research results into clinical practice, in order to provide best treatment for cancer patients in accordance with the principles of the precision medicine.
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Ethical issues in (pharmaco)genetics
(2019-10)
Apart from genetic testing for diagnostic purposes, application of genetics in human medicine encompasses genetic interventions and pharmacogenetical testing which are becoming more frequently utilized in clinical practice, as well as genetic studies employed in the process of research and drug development. It’s been widely known and accepted that application of a drug in equal dosing regimens for treatment of the same diagnosis in different patients, doesn’t produce equal results regarding achievement of a therapeutic effect and/or occurrence of side effects. Investigating the genetic cause for interindividual variations in patients’ drug response and toxicity, pharmacogenetics holds valuable prognostic and predictive value in tailoring the pharmacological treatment of various diseases according to the principles of precision medicine. But, just as any other medical testing, genetic analyses impose ethical risks which in this case are even more serious due to the following specific features of these tests and the obtained data: the “mutual” ownership of the genetic information by individuals from the same family, the lack of precise phenotype-genotype correlation and the influence of epigenetic and environmental factors on the phenotypic expression of genetic information, the balance between the right of an individual “to know” and the right “to not know” as well as the enormous potential for discrimination. The rapid advancement of high throughput technologies delivering a mass of detailed data on an individual’s genome introduces a lot of advantages in scientific and clinical applications, but also threatens with a tremendous risk for misuse of these data in various settings. The lecture discusses the fundamental ethical principles applicable to genetic analyses/studies including respect of the individual’s autonomy and privacy and commitment to providing confidentiality, beneficence and justice. The informed consent as well as the levels of anonymization in genetic testing as measures to satisfy the above mentioned principles will be addressed. Special emphasis will be placed on the ethical issues regarding orphan and rescued drugs emerging in the pharmacogenetical testing within clinical studies in drug research and development. Philosophers of science claim that science is morally neutral, it is actually the use and implementation of science that can have positive or negative impact. Hence, it is crucial to understand that achievement of our aim for humane application of (pharmaco)genetics can only be accomplished if technological and clinical advances in this field advance at a similar rate with the corresponding ethical considerations.
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Pharmacogenetic testing in optimization of treatment with statins
(2018-10)
Statins are a class of drugs that have been widely prescribed nowadays for treating hypercholesterolemia and thus prevent the risk of atherosclerotic cardiovascular events and consecutive mortality. Unfortunate ly, the patient’s compliance with treatment is frequently compromised by the high incidence of adverse effects including hepatotoxicity, myotoxicity, increased risk for diabetes mellitus etc. The expansion of the precision medicine concept in pharmacology has introduced pharmacogenetic testing as a potential predictive strategy in statins pharmacotherapy. A thorough literature survey was performed using the PubMed database on the published data in English language in the period 2000-2017, regarding genotype-phenotype associations in statin-induced toxicity, identifying a growing body of evidence supporting the need for pharmacogenetic approach in treatment with statins. Polymorphisms in the genes coding for the CYP450 enzymes: CYP2D6, DYP2D9, CYP3A4 and drug transporter genes like ABCB1, ABCG2 and SLCO1B1 appear to be responsible for the variable re sponse and toxicity of statins. But, many studies highlight the importance of drug interactions and epi genetics in modifying the response towards this class of drugs metabolized via pathways shared by the majority of pharmaceutical agents. With the rapid development of molecular techniques accompanied by a dramatic cost reduction in genetic testing, it can be easily anticipated that pharmacogenetic patient profiling will soon become standard of care in designing the optimal statin treatment either as a monotherapy or in combination with other phar maceuticals.
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Pharmacogenomics in cancer management
(2018)

Hiljadnikova-Bajro, Marija

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