0000000000181867
AUTHOR
Kaspars Megnis
Pituispheres Contain Genetic Variants Characteristic to Pituitary Adenoma Tumor Tissue
The most common type of pituitary neoplasms is benign pituitary adenoma (PA). Clinically significant PAs affect around 0.1% of the population. Currently, there is no established human PA cell culture available and when PA tumor cells are cultured they form two distinct types depending on culturing conditions either free-floating aggregates also known as pituispheres or cells adhering to the surface of cell plates and displaying mesenchymal stem-like properties. The aim of this study was to trace the origin of sphere-forming and adherent pituitary cell cultures and characterize the potential use of these surgery derived cell lines as PA model. We carried out a paired-end exome sequencing of …
Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
Acromegaly is a disease mainly caused by pituitary neuroendocrine tumor (PitNET) overproducing growth hormone. First-line medication for this condition is the use of somatostatin analogs (SSAs), that decrease tumor mass and induce antiproliferative effects on PitNET cells. Dopamine agonists (DAs) can also be used if SSA treatment is not effective. This study aimed to determine differences in transcriptome signatures induced by SSA/DA therapy in PitNET tissue. We selected tumor tissue from twelve patients with somatotropinomas, with half of the patients receiving SSA/DA treatment before surgery and the other half treatment naive. Transcriptome sequencing was then carried out to identify diff…
Adenohpofīzes adenomu funkcionālais profils un to ietekmējošie faktori
Adenohipofīzes adenomas ir labdabīgi intrakraniāli endokrīnie audzēji ar potenciāli augstu prevalenci populācijā. Klīniskajā praksē ir attīstītas vairākas adenomu ārstniecības terapijas, taču tās ne vienmēr ir efektīvas. Darbā veikta adenohipofīzes adenomu funkcionalitāti ietekmējošo faktoru raksturošana. Tika noteikti somatotrofajām, laktotrofajām un nehormonālajām adenomām raksturīgi gēnu ekspresijas profili, kā arī funkcionālajiem tipiem nespecifiski somatostatīna un dopamīna receptoru klasteri, kas norāda uz konkrēto receptoru mijiedarbību adenomu darbības ietekmēšanā. Tika konstatēts, ka hormonu sintēzi ierosinošie faktori pozitīvi ietekmē adenomu funkcionālo darbību nomācošo gēnu eksp…
First Report on the Latvian SARS-CoV-2 Isolate Genetic Diversity
Remaining a major healthcare concern with nearly 29 million confirmed cases worldwide at the time of writing, novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 920 thousand deaths since its outbreak in China, December 2019. First case of a person testing positive for SARS-CoV-2 infection within the territory of the Republic of Latvia was registered on 2nd of March 2020, 9 days prior to the pandemic declaration by WHO. Since then, more than 277,000 tests were carried out confirming a total of 1,464 cases of coronavirus disease 2019 (COVID-19) in the country as of 12th of September 2020. Rapidly reacting to the spread of the infection, an ongoing sequenci…
Evaluation of the Possibility to Detect Circulating Tumor DNA From Pituitary Adenoma
Objective: Circulating free DNA (cfDNA) in general and circulating tumor DNA (ctDNA) in particular is becoming an increasingly used form of liquid biopsy biomarkers. In this study, we are investigating the ability to detect ctDNA from the plasma of pituitary adenoma (PA) patients. Design: Tumor tissue samples were obtained from planed PA resections, before which blood plasma samples were taken. Somatic variants found in PA tissue samples were evaluated in related cfDNA, isolated from plasma samples. Methods: Sanger sequencing, as well as previously obtained whole-exome sequencing data, were used to evaluate somatic variants composition in tumor tissue samples. cfDNA was isolated from the sa…
Purīnerģiskā divpadsmitā receptora 181. pozīcijas randomizēto variantu funkcionālā aktivitātes izpēte
Kopsavilkums Darba gaitā tika izvērtēta P2Y12R 181. pozīcijā esošās glutamīnskābes loma receptora mijiedarbībā ar agonistu ADP un antagonistu OSI-10110. P2Y12R varianti ar mutaģenizētu 181. pozīciju tika ekspresēti S. cerevisiae šūnās un aktivēti ar ADP, OSI-10110 un AR-C66096. Tika konstatēts, ka Glu181 aizvietošana ar pēc fizikāli ķīmiskās dabas līdzīgām aminoskābēm, var dažādi ietekmēt receptora un liganda mijiedarbību. Ar QSAR datu analīzi, tika konstatēts, ka P2Y12R Glu181 mijiedarbībā ar ADP un OSI-10110, būtiskas ir aminoskābes hidrofīlās un elektriskās īpašības. Glu181 mijiedarbību ar OSI-10110 nedaudz arī ietekmē aminoskābes fleksibilitāte. OSI-10110 uzrāda zemāku ietekmi uz ADP iz…
Hipofīzes audzēju patoģenēzes biomolekulāro mehānismu izpēte
Darbā analizētas hipofīzes šūnu kultūru biomolekulārās īpašības un no hipofīzes izcelsmes šūnām brīvās DNS molekulu klātbūtne pacientu asins plazmā. Tika konstatēts, ka viena no šūnu kultūrām ir multipotentas mezinhimāli stromālās šūnas, kas visticamāk nav galvenā PitNET šūnu populācija, bet, iespējams, tai ir audzēja darbību atbalstoša loma. Otra šūnu kultūra ir hipofīzes sfēru veidojošas šūnas, kuras visticamāk, veido audzēja galveno audu masu. Tām bija kopīgas ģenētiskās iezīmes ar galveno audzēja masu. Analizējot pacientu šķidrās biopsijas, tika atklāts, ka PitNET audu paraugos atrastās somatiskās mutācijas ar dažādu jutību ir konstatējamas arī šūnu brīvajā DNS. Atslēgvārdi: hipofīzes n…
Selective enrichment of heterotrophic nitrifiers <em>Alcaligenaceae</em> and <em>Alcanivorax</em> spp. from industrial wastewaters
Removal of nitrogen from wastewaters (WW) represents a global problem. The low nitrification rate during WW treatment is often caused by ecotoxicity. This problem is attributed mostly to the industrial WW. Our study was focused on the testing of industrial WW and activated sludge (AS) with the aim to reveal the abundance of nitrifiers and increase their biomass, thus, providing the additional step, i.e., bioaugmentation, within the technological process of WW treatment. Plating of AS on the selective solidified media designated for the 1st and 2nd nitrification stages, resulted in the shift in bacterial community structure with dominated Alcaligenaceae and Alcanivorax for the 1st stage, and…