Experimental Oncology, 2016, № 1

Inhibition of malignant potential and expression of proteins associated with epithelial-mesenchymal transition in Lewis lung carcinoma cells transduced with murine ifn-β gene in recombinant baculovirus

Fri, 01 Jan 2016 00:00:00 GMT

Inhibition of malignant potential and expression of proteins associated with epithelial-mesenchymal transition in Lewis lung carcinoma cells transduced with murine ifn-β gene in recombinant baculovirus Lykhova, O.; Kovalova, O.; Bezdenezhnykh, N.; Adamenko, I.; Vorontsova, A.; Strokovska, L.; Kudryavets, Yu. Aim: To analyze biological characteristics. malignant potential and expression of proteins associated with epithelial mesenchynal transition in murine lung carclnoma cells transduced with intertcron-beta (ifn-β) gene in baculovirus vector. Materials and Methods: The study was perforated on Lewis lung carcinoma (LL) cells transduced with ifn-β gene in recombinant baculovirus vector. Biological characterlstics of the LL cells were studied with the use of standard cell culture method, cytogenetic and immunocytochemical assays. Resutes: Recombinant baculmirus-mediated transduction of LL cells with ifn-β gene resulted in siguﬁcant decrease of cell growth rate and density both in complete and serum-foee medium. Also. LL cells transduction with ifn-β gene signiﬁcantly inhﬂtited cell migration in vitro. Transduction of LL cells by baculovirus vector with or withoot ifn-β gene caused signiﬁcant genotoxic effect in these cells. Furthermore. ifn-β gene transfer to lung carcinoma cells resulted in signiﬁcant increase of nuclear expression of p19ARE (p < 0.01). p21WAFI (p < 0.001). cytoplasmic expression of E-cadherin (p < 0.005) and inhibition of transcription factors of epithelial-mesenchymal transition (EMT) Tmist (p < 0.005) and Slug (p < 0.00 I) expression. Conclusions; Transduction with ifn-β gene of LL cells in recombinant baculovirus resulted in aquirement of less malignant phenotype in vitro and suppressed expression ofproteins associated with EMT.

miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation

Fri, 01 Jan 2016 00:00:00 GMT

miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation Hashemi, M.; Sanaei, S.; Rezaei, M.; Bahari, G.; Hashemi, S.M.; Mashhadi, M.A.; Taheri, M.; Ghavami, S. Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on breast cancer (BC) risk. Materials and Methods: This case-control study conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of miR608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Our findings showed that GC genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.28–0.88, p = 0.018) compared to CC genotype. Furthermore the G allele decreased the risk of BC (OR = 0.53, 95%CI 0.30–0.92, p = 0.024). No significant association was found between miR-609 genotypes and clinicopathological characteristics of BC patients (p > 0.05). Conclusion: Our findings indicate that miR-608 polymorphism might be associated with decreased risk of BC in an Iranian subpopulation. Further large-scale studies with different ethnicities are needed to verify our findings.

Superoxide- and no-dependent mechanisms of antitumor and antimetastatic effect of L-arginine hydrochloride and coenzyme Q₁₀

Fri, 01 Jan 2016 00:00:00 GMT

Superoxide- and no-dependent mechanisms of antitumor and antimetastatic effect of L-arginine hydrochloride and coenzyme Q₁₀ Burlaka, A.P.; Ganusevich, I.I.; Golotiuk, V.V.; Vovk, A.V.; Lukin, S.M. Aim: To study the redox-dependent mechanism of antiradical, antitumor and antimetastatic action of L-arginine hydrochloride (L-Arg) and coenzyme Q₁₀ (CoQ₁₀) in vivo. Materials and Methods: The study was performed on С57Вl mice with transplanted Lewis lung carcinoma treated by intraperitoneal injections of L-Arg at low or high doses (60 and 360 mg/kg body weight), CoQ₁₀ (0.2 and 1.2 mg/kg body weight) or their combinations. Electron paramagnetic resonance was applied for analysis of mitochondrial electron transport chain, СoQ₁₀ levels, free iron (FI), the level of NO, and the rate of superoxide radical generation. The activity of matrix metalloproteinase (MMP)-2 and -9 in tumor tissue was determined by zymography method in polyacrylamide gel. Results: Administration of L-Arg at high doses caused an inhibition of tumor growth by 48 ± 8.0%, increase of superoxide radical generation rate and NO levels to a value of 1.23 ± 0.14 аnd 2.26 ± 0.31 nm/g tissue · min, and decreased activity of MMP-2 and -9 (3.55 ± 0.8 and 4.8 ± 1.0 r.u., respectively). Treatment with L-Arg at low doses stimulated tumor growth and increased the levels of MMP-2 and -9 activities (8.44 ± 2.7 and 9.8 ± 3.1 r.u., respectively). Administration of СoQ₁₀ at high doses significantly decreased superoxide radical generation rate to the values of 0.44 ± 0.09 nm/g tissue · min, levels of free iron and NO, and caused tumor growth inhibition by 54 ± 11.3%. The combined use of L-Arg and СoQ₁₀ at high doses caused tumor growth inhibition by 51 ± 7.4% compared to Lewis lung carcinoma-bearing untreated animals (р < 0.05). Conclusions: Administration of L-Arg and СoQ₁₀ caused the dose-dependent effect on the rate of generation of superoxide radicals, level of ubisemyquinone, complexes NOFeS-proteins, levels of FI and NO. L-Arg at low doses positively modulated MMP-9 activity that promoted tumor progression. Upon combined use of L-Arg and СoQ₁₀, superoxide radicals and NO form the redox state that causes decrease of MMP-2, -9 activities with consequent inhibition of tumor invasion and metastasis.

70th Anniversary Of The Lviv Scientific School Of Oncology

Fri, 01 Jan 2016 00:00:00 GMT

70th Anniversary Of The Lviv Scientific School Of Oncology Bilynsky, B.T.; Shparyk, Ya.V.; Mryglotsky, M.M.; Lukavetskyy, N.O.; Volod’ko, N.A.; Litvinyak, R.I. Contemporary development of scientific thought is fostered not by separate people but is a purposeful activity of a group of likeminded people armed with progressive ideas and modern technical equipment. Such schools appeared and work actively in the majo rity of research and educational establishments, clinics, and universities. The Lviv school established in 1945 by Professor H.P. Kovtunovych and developed by Professor A.I. Hnatyshak and his disciples can serve as an example of a successful school of oncology that continues its activity and yields scientific results. This school appeared not out of the thin air. Medieval Lviv could boast of the first university on the territory of the present-day Ukraine. Many discoveries and endeavors that made a beneficial impact on the development of medicine in Eastern Europe were made in this city. For historical reasons, the city of Lviv used to belong to different state formations (Austria-Hungary, Poland, the USSR; now it is a part of Ukraine), which could not but reflect on the staffing of doctor-researchers. This process acquired a special intensity in 1939–1945 when the research staff of the university changed substantially. Then, in 1945, H.P. Kovtunovych, the disciple of the prominent oncologist N.N. Petrov, came to Lviv and brought the ideas of St.-Petersburg oncology to the Lviv ground. The Lviv school was influenced by the two times Nobel Prize winner Marie Skłodowska Curie, who facilitated the initiation of oncological radiology in Lviv. The article contains data on research done by the disciples of Professors H.P. Kovtunovych and A.I. Hnatyshak. The first ever teaching chair of oncology in the USSR was founded in Lviv (1966), as well as the first Ukrainian hospice — an institution for palliative care for the oncological patients. The Lviv oncology center is one of the biggest and best-equipped oncology centers in Ukraine. An organic combination of theory and clinical practice has always been the guiding principle of the Lviv school of oncology. Presently, the Lviv school of oncology unites six doctors of sciences, a large collective of educators and researchers, as well as practitioners of the center of oncology. The school maintains close scientific and practical ties with oncologists of Ukraine as well as with leading oncological centers of Europe and America.