BackgroundIncreasing evidence is demonstrating that a patient’s unique genetic profile can be used to detect the disease’s onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine (PM) and pharmacogenomics (PG) in clinical practice. Here we investigated the perceptions of students from different universities in Bosnia and Herzegovina (BH) towards PG/PM as well as related ethical, legal, and social implications (ELSI). This descriptive, cross-sectional study is based on the survey of 559 students from the Faculties of Medicine, Pharmacy, Health Studies, Genetics, and Bioengineering and other study programs.ResultsOur results showed that 50% of students heard about personal genome testing companies and 69% consider having a genetic test done. A majority of students (57%) agreed that PM represents a promising healthcare model, and 40% of students agreed that their study program is well designed for understanding PG/PM. This latter opinion seems to be particularly influenced by the field of study (7.23, CI 1.99–26.2, p = 0.003). Students with this opinion are also more willing to continue their postgraduate education in the PM (OR = 4.68, CI 2.59–8.47, p < 0.001). Furthermore, 45% of students are aware of different ethical aspects of genetic testing, with most of them (46%) being concerned about the patient’s privacy.ConclusionsOur results indicate a positive attitude of biomedical students in Bosnia and Herzegovina towards genetic testing and personalized medicine. Importantly, our results emphasize the key importance of pharmacogenomic education for more efficient translation of precision medicine into clinical practice.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0182-2) contains supplementary material, which is available to authorized users.

Chemotherapy resistance is one of the major challenges in cancer treatment, including leukemia. A massive array of research is evaluating combinations of drugs directed against different intracellular signaling molecules to overcome cancer resistance, increase therapy effectiveness, and decrease its adverse effects. Combining chemicals with proven safety profiles, such as drugs already used in therapy and active substances isolated from natural sources, could potentially have superior effects compared to monotherapies. In this study, we evaluated the effects of metformin and thymoquinone (TQ) as monotherapy and combinatorial treatments in chronic myeloid leukemia (CML) cell lines sensitive and resistant to imatinib therapy. The effects were also evaluated in primary monocytic acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) cells. Both compounds induced a dose- and time-dependent decrease of viability and proliferation in tested cells. Metformin had similar IC50 values in imatinib-sensitive and imatinib-resistant cell lines. IC50 values of TQ were significantly higher in imatinib-resistant cells, but with a limited resistance index (2.4). Synergistic effects of combinatorial treatments were observed in all tested cell lines, as well as in primary cells. The strongest synergistic effects were observed in the inhibition of imatinib-resistant cell line proliferation. Metformin and TQ inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and induced apoptosis in tested cell lines and primary cells. The enhanced effects of combinatorial treatments on the induction of apoptosis were more dominant in imatinib-resistant compared to imatinib-sensitive CML cells. Primary cells were more sensitive to combinatorial treatments compared to cell lines. A combination of 1.25 mM metformin and 0.625 µM TQ increased the levels of cleaved poly (ADP-ribose) polymerase (PARP), decreased the levels of proliferation regulatory proteins, and inhibited protein kinase B (Akt) and NF-κB signaling in primary CLL cells. This study demonstrates that combinatorial treatments of imatinib-resistant malignant clones with metformin and TQ by complementary intracellular multi-targeting represents a promising approach in future studies.

Background Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Methods Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Results Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], padd = 0.025; B = 0.079, 95% CI [0.006, 0.150], padd = 0.033, respectively) in T2D, and with HbA1c (B = 0.034, 95% CI [0.003, 0.065], pdom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = −0.17, 95% CI [−0.03, −0.002], padd = 0.030) and HbA1c (B = 0.03, 95% CI [0.002, 0.06], pdom = 0.040) in non-drug-treated T2D. Conclusions We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA1c levels in Bosnia and Herzegovina’s population.

Head and neck cancers (HNC) occur in the upper aerodigestive tract and are among the most common cancers. The etiology of HNC is complex, involving many factors, including excessive tobacco and alcohol consumption; over the last two decades, oncogenic viruses have also been recognized as an important cause of HNC. Major etiological agents of nasopharynx carcinoma and oropharyngeal carcinoma include Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), both of which are able to interfere with cell cycle control. Additionally, the association of hepatitis C and hepatitis B infection was observed in oral cavity, oropharyngeal, laryngeal, and nasopharyngeal cancers. Overall prognoses depend on anatomic site, stage, and viral status. Current treatment options, including radiotherapy, chemotherapy, targeted therapies and immunotherapies, are distributed in order to improve overall patient prognosis and survival rates. However, the interplay between viral genome sequences and the health, disease, geography, and ethnicity of the host are crucial for understanding the role of viruses and for development of potential personalized treatment and prevention strategies. This review provides the most comprehensive analysis to date of a vast field, including HNC risk factors, as well as viral mechanisms of infection and their role in HNC development. Additionally, currently available treatment options investigated through clinical practice are emphasized in the paper.

Chronic myeloid leukemia (CML) is a myeloproliferative haematological malignancy characterized by constitutive activation of BCR-ABL1 tyrosine kinase in the majority of patients. BCR-ABL1 expression activates signaling pathways involved in cell proliferation and survival. Current treatment options for CML include tyrosine kinase inhibitors (TKI) with resistance as a major issue. Various treatment options for overcoming resistance are being investigated. Among them, phytochemical curcumin could play an important role. Curcumin has been found to exhibit anti-cancerous effects in various models, including CML, through regulation of multiple molecular signaling pathways contributing to tumorigenesis. We have evaluated curcumin’s effects on imatinib-sensitive LAMA84S and K562, as well as imatinib-resistant LAMA84R cell lines. Our results indicate a significant dose-dependent decrease in cell viability and proliferation of imatinib-sensitive and imatinib-resistant cell lines after curcumin treatment. Suppression of key signaling molecules regulating metabolic and proliferative events, such as Akt, P70S6K and NF-kB, was observed. Increased expression of caspase-3 suggests the potential pro-apoptotic effect of curcumin in the imatinib-resistant CML model. Additional in silico molecular docking studies revealed binding modes and affinities of curcumin with different targets and the results are in accordance with in vitro findings. Altogether, these results indicate the potential role of curcumin in the treatment of CML.