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One of the important medical problems consists in the prevalence and incidence of cervical cancer, implementation of innovative technologies in the diagnostics and treatment of this pathology. Every six months, half a million women around the globe are taken ill by this disease, and 270 thousand women die of it. Undoubtedly, the major burden of this disease falls on developing countries. However, for economically developed countries with a well organized cervical screening, this problem remains topical too. In European countries, cervical screening allowed to significantly reduce the cervical cancer incidence in 80-90s of the previous century, for instance, in Great Britain, Sweden, and Finland. However, even in these countries, for the past 15-20 years, the number of women suffering from cervical cancer has not decreased. The main reason lies in epidemiological, social, and ecologic peculiarities of the modern world. If modern tendencies of cervical cancer incidence growth retain, then an annual number of people with cervical cancer may reach 1 million by 2050. Based on the WHO assessment, there exist all prerequisites for cervical cancer elimination. Vaccination allows creating a sufficiently powerful collective immunity against HPV. There exist quite specific and sensitive methods for diagnostics and treatment of cervical precancer, which are being improved every year. We are witnessing a change of diagnostic paradigm of cervical screening. The co-testing strategy came to replace the traditional PAP testing. Increased sensitivity and specificity of cytologic testing is achieved using the method of liquid-based cytology together with HPV testing. Initial HPV screening provides promising results, ensuring wide coverage of female population thanks to the possibility of independent sampling. In Ukraine, cervical cancer incidence constituted 4,157 people in 2016-2017, while the death rate amounted to 1,757 women. The mortality rate up to one year constitutes 16.7%. It is worth noting that in 2017, the increase in cervical cancer incidence (21.5 against 20 per 100 thousand of the female population) and mortality (9 against 8.7 respectively) was recorded. Every day in Ukraine, 6 women die of this disease. And this happens despite the fact that we do have the infrastructure for opportunist cervical screening. Implementation of a new generation cervical screening will enable revolutionary HPV prevention, improved diagnostics, and treatment of cervical precancer.

YAROSLAV SHPARYK. MEDICINE IN HOLY BOOK

«MULTIFUNCTIONAL NANOMATERIALS FOR BIOLOGY AND MEDICINE: MOLECULAR DESIGN, SYNTHESIS AND APPLICATION» / EDITED BY R.S. STOIKA, CORRESPONDING MEMBER OF NAS OF UKRAINE Використання наноматеріалів для медицини і біотехнології з кожним роком стає все більш актуальним. Це пов’язане із низь- кою адресністю дії традиційних лікарських препаратів, що при- зводить до негативних побічних ефектів їхньої дії, а також зі швидким розвитком резистентності клітин лікованого організму для застосованих ліків, що призводить до зниження ефектив- ності їхньої дії. Різні наноплатформи для доставки ліків та інших біологічно активних речовин, наприклад, нуклеїнових кислот, покликані вирішити зазначені проблеми, причому саме багато- функціональність цих платформ є тут центральним аспектом. У рецензованій монографії зроблено узагальнення сучасного стану створення і використання багатофункціональних наноматеріалів для біології і медицини, а також проаналізовано головні досягнен- ня вчених України, що працюють у цьому напрямку досліджень. Структура монографії побудована за прийнятим зараз викладом матеріалів, коли окремі глави пишуться спеціалістами, які є визна- ними лідерами у розробці тієї чи іншої наукової проблеми.

Ras association domain family protein 1A (RASSF1A) is a tumor suppressor gene silenced in cancer. Here we report that RASSF1A is a novel regulator of intestinal inflammation as Rassf1a(+/-) , Rassf1a(-/-) and an intestinal epithelial cell specific knockout mouse (Rassf1a (IEC-KO) ) rapidly became sick following dextran sulphate sodium (DSS) administration, a chemical inducer of colitis. Rassf1a knockout mice displayed clinical symptoms of inflammatory bowel disease including: increased intestinal permeability, enhanced cytokine/chemokine production, elevated nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB) activity, elevated colonic cell death and epithelial cell injury. Furthermore, epithelial restitution/repair was inhibited in DSS-treated Rassf1a(-/-) mice with reduction of several makers of proliferation including Yes associated protein (YAP)-driven proliferation. Surprisingly, tyrosine phosphorylation of YAP was detected which coincided with increased nuclear p73 association, Bax-driven epithelial cell death and p53 accumulation resulting in enhanced apoptosis and poor survival of DSS-treated Rassf1a knockout mice. We can inhibit these events and promote the survival of DSS-treated Rassf1a knockout mice with intraperitoneal injection of the c-Abl and c-Abl related protein tyrosine kinase inhibitor, imatinib/gleevec. However, p53 accumulation was not inhibited by imatinib/gleevec in the Rassf1a(-/-) background which revealed the importance of p53-dependent cell death during intestinal inflammation. These observations suggest that tyrosine phosphorylation of YAP (to drive p73 association and up-regulation of pro-apoptotic genes such as Bax) and accumulation of p53 are consequences of inflammation-induced injury in DSS-treated Rassf1a(-/-) mice. Mechanistically, we can detect robust associations of RASSF1A with membrane proximal Toll-like receptor (TLR) components to suggest that RASSF1A may function to interfere and restrict TLR-driven activation of NFκB. Failure to restrict NFκB resulted in the inflammation-induced DNA damage driven tyrosine phosphorylation of YAP, subsequent p53 accumulation and loss of intestinal epithelial homeostasis.

Aim: To investigate the association between tumor protein 53 (TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease (IBD) development., Methods: Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer (CRC) patients. A single nucleotide polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine (Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers, including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood., Results: The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls (53%) and less common in patients (31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients., Conclusion: The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development.