Tamašauskas, Arimantas

Background: Pituitary adenomas are slow-growing tumors that originate from the anterior part of the pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long non-coding RNA (lncRNA) that has been implicated in the regulation of cell proliferation, gene expression, apoptosis, differentiation, and cell cycle transition in various tumors, including pituitary adenomas (PA).

Objective: To evaluate the impact of MALAT1 gene variants (rs3200401, rs619586, and rs1194338) and immunohistochemical markers (Ki-67 and p53) on the susceptibility and clinical characteristics of PA.

Methods: a case-control study included patients with PA and age- and gender-matched controls. PA diagnosis was confirmed through MRI/CT imaging and/or histopathological examination. DNA was extracted from peripheral blood samples, and three MALAT1 variants (rs3200401, rs619586, and rs1194338) were genotyped using TaqMan® real-time PCR. The expression of Ki-67 and p53 were evaluated immunohistochemically using digital image analysis. Statistical analyses included chi-square tests to compare genotype and allele distributions, logistic regression to estimate PA risk (odds ratios, 95% confidence intervals), and nonparametric tests for biomarker evaluation.

Results: Among 390 participants (145 PA and 245 controls), only the MALAT1 rs619586 variant showed statistically significant associations after Bonferroni correction (p < 0.016). The rs619586 G allele was more frequent in PA patients than in controls (4.1% vs. 0.8%, p = 0.001) and increased the odds of developing PA by 4.1-fold under the additive model (OR = 4.139, 95% CI: 1.365- 12.551, p = 0.012). The G allele remained significantly associated across several clinical subgroups, including microadenomas, macroadenomas, invasive PAs, and PAs with recurrence (p ≤ 0.015). In PA tissues, p53 H-scores were higher in macroadenomas compared with microadenomas (p = 0.047), and patients with the rs619586 AA genotype showed significantly higher p53 expression than those with the AG genotype (p = 0.008). A moderate positive correlation was observed between Ki-67 LI and p53 expression (ρ = 0.268, p = 0.035).

Conclusions: MALAT1 rs619586 G allele is significantly associated with an increased risk of PA and its more aggressive clinical features, including invasiveness and recurrence. These findings suggest that rs619586 may serve as a potential genetic marker linked to PA susceptibility. Additionally, the observed relationship between p53 expression and tumor proliferation highlights its potential role in PA tumorigenesis. Further studies are needed to confirm these associations and clarify the underlying molecular mechanisms.

Nutukimas - viena aktualiausių dabartinės visuomenės problemų, neigiamai veikianti daugelį organizmo sistemų ir trikdanti sergančiojo šia liga gyvenimo kokybę, darbingumą bei trumpinanti gyvenimą. Tai - metaboliškai aktyvi ir recidyvuojanti liga, kurios metu kūno masė didėja riebalinio audinio sąskaita. Nutukimą kaip ligą Amerikos medicinos asociacija oficialiai pripažino 2013 metais. Nutukimas pastaruoju metu yra labiausiai aptarinėjama tema tiek medicinos, tiek plačiojoje visuomenėje. Kalbant apie nutukimą, dažnai ši būklė siejama su asmeniniu kaltės priskyrimu: „reikia tik noro“, „reikia suimti save į rankas“ ir t. t. Įvairiais istoriniais laikotarpiais požiūris į žmogaus kūno formas keitėsi nuo Rubenso tipo moterų iki anoreksinių mados manekenių formų. Menamų kūno formų standartų neatitinkantis žmogus gali būti pavadintas putliu, stambiu, apkūniu, didelio dydžio ar net storuliu ar apsileidusiu. Medicinos bendruomenėje vyrauja terminai: antsvoris, hipotalaminis, pilvinis, centrinio tipo, kušingoidinis, morbidinis nutukimas ir kt. Nutukimas turi kompleksines pasekmes - skatina lėtines ligas, galinčias sutrumpinti žmogaus amžių 10-15 metų. Per pastaruosius 5 dešimtmečius nutukimo paplitimas pasaulyje padidėjo daugiau nei 3 kartus, ir dabar tai įvardijama kaip nutukimo pandemija. Klinikinėje praktikoje nustatomos įvairiausios nutukimo priežastys - nuo genetinių (Prader-Willi sindromas, Aistrom sindromas, LEPR (leptino receptoriaus) ar LEP (leptino) geno mutacijos ir kt.), endokrininių (hipotirozė, hiperkorticizmas, hipogonadizmas ir kt.) iki valgymo priklausomybių. Skirtingos yra ir nutukusių kūno formos bei kūno kompozicija. Todėl kūno masės indeksas (KMI) klinikiniu požiūriu jau nebetenka prasmės. KMI tikslinga naudoti populiaciniams, palyginamiesiems tyrimams. Statistiniais duomenimis (HIS Lietuva, Eurostat, 2019-2022 m.), pagal KMI nutukusių suaugusių Lietuvoje buvo 21-23 proc. Skaičiuojama, kad apie 60 proc. suaugusiųjų Lietuvoje turi antsvorio ar yra nutukę. Tai - tik statistika, neatspindinti konkrečios individo būklės. 2025 m. pasaulio 58 ekspertų grupė, atstovaujanti įvairioms medicinos specialybėms ir šalims, išanalizavo turimus įrodymus ir, pritarus 75 medikų ir pacientų organizacijoms, rekomendavo klasifikaciją, kurioje išskiriamas ikiklinikinis ir klinikinis nutukimas. Pagal epidemiologinius ir klinikinius duomenis, nutukimas susijęs su daugiau nei 200 skirtingų ligų ir sveikatos sutrikimų. [...]

Background: Pituitary tumor-transforming gene 1 (PTTG1) is a proto-oncogene implicated in pituitary neuroendocrine tumors (PitNETs) pathogenesis through regulation of the cell cycle, genomic instability, and angiogenesis. Overexpression of PTTG1 promotes tumor growth, but the impact of its genetic variants in PitNETs size is insufficiently defined.

Objective: To evaluate the impact of PTTG1 gene variants (rs1895320, rs2910200, and rs6882742), circulating PTTG1 levels, and immunohistochemical markers (Ki-67 and p53) on PitNETs susceptibility and clinical features.

Methods: case–control study included patients with PitNETs and age- and gender-matched controls. Diagnosis of PitNETs was confirmed by MRI/CT and/or histopathology. Genomic DNA was extracted from peripheral blood, and three PTTG1 variants (rs1895320, rs2910200, rs3811999) were genotyped using TaqMan® real-time PCR assays. Serum PTTG1 levels were measured by ELISA, while Ki-67 and p53 expression were assessed immunohistochemically with digital image analysis. Statistical analyses included chi-square comparisons of genotype/allele distributions, logistic regression for PitNETs risk (odds ratios, 95% CI), and nonparametric tests for biomarker evaluation.

Results: A total of 340 participants were enrolled, comprising 120 PitNET patients and 220 controls. Median age (53.5 vs. 54 years) and gender distribution did not differ between the groups. Among patients, 35% had microadenomas and 65% had macroadenomas. Logistic regression revealed that the PTTG1 rs3811999 TT genotype was associated with increased odds of microadenoma occurrence (OR = 2.53, 95% CI: 1.17-5.48, p = 0.018). The PTTG1 rs2910200 TT genotype and T allele were significantly more common in tumors with lower proliferative activity Ki-67 LI < 3% (p = 0.013 and p = 0.004), suggesting a potential association with reduced proliferation. In contrast, the rs3811999 TT genotype and T allele were more frequent in tumors with Ki-67 LI > 3% (p = 0.015 and p = 0.011), indicating a relationship with higher proliferative potential. Macroadenomas exhibited significantly higher p53 H-scores than microadenomas (27.34 vs. 16.00, p = 0.012), while no associations were observed with gender, invasiveness, activity, or recurrence.

Conclusions: Results suggest that PTTG1 rs3811999 may influence tumor size or growth pattern, possibly contributing to early tumorigenesis. We can hypothesize that the variant may alter gene expression or protein function, thereby predisposing to PitNETs development at an earlier stage (microadenomas). Future research should integrate molecular studies with larger genetic datasets to clarify how PTTG1 variants contribute to PitNETs’ pathophysiology.

Pituitary adenoma (PA) is one of the most common brain tumors, yet its pathogenesis remains unclear. PA can be categorized by size into microadenomas (<10 mm) and macroadenomas (≥10 mm). While microadenomas usually present with mild or isolated endocrine abnormalities, macroadenomas are more likely to cause visual impairment, headache, hypopituitarism, and local invasiveness due to mass effect on surrounding structures. Molecular biomarkers indicate biological and pathological processes or therapeutic responses, offering valuable insights for diagnosis and prognosis. CXCL13, a homeostatic chemokine, primarily induces B-cell chemotaxis, lymphoid tissue organization, and the recruitment of immune cells. CXCL13 gene variants, particularly those affecting expression or function, may influence PA risk, size, invasiveness, and treatment response. Understanding the genetic role of CXCL13 could support personalized treatments and improve prognostic tools for PA management. A case-control study enrolled 170 PA patients and 230 healthy controls. DNA samples from peripheral blood leukocytes were purified by the DNA salting-out method. Singlenucleotide variants (rs355687, rs1566485) were determined using real-time polymerase chain reaction (RT-PCR). Statistical data analysis was performed using the “IBM SPSS Statistics 30.0” program. We found that CXCL13 rs355687 TT genotype vs. CC+CT was associated with about 2.5-fold decreased odds of PA occurrence under the recessive model (OR = 0.406, 95% CI: 0.169-0.974, p = 0.043) and CXCL13 rs1566485 CA genotype vs. CC+AA was associated with about 1.5-fold increased odd of PA occurrence under the overdominant model (OR = 1.552, 95% CI: 1.041-2.312, p = 0.031). Binary logistic regression analysis revealed that CXCL13 rs1566485 CA genotype vs. CC+AA was associated with about 1.8-fold increased odds of macro PA occurrence under the overdominant model (OR = 1.751, 95% CI: 1.114-2.751, p = 0.015). Conclusions: Our findings show that the CXCL13 rs355687 TT genotype significantly reduces the odds of PA occurrence, suggesting a potential protective effect. In contrast, the rs1566485 CA genotype increases the risk of PA development and demonstrates an even stronger association with macroadenoma formation. These results indicate that CXCL13 genetic variation, particularly rs1566485 CA, may contribute to PA susceptibility and tumor growth dynamics.

Purpose: To determine the association between FGFR4 (rs351855 and rs7708357) gene polymorphisms and serum levels association with pituitary adenoma (PA). Methodology: A case-control study was conducted involving 279 subjects divided into two groups: the control group (n = 199) and a group of PA (n = 80). The genotyping of FGFR4 rs351855 and rs7708357 were carried out using the real-time polymerase chain reaction method. The serum concentration of FGFR was measured using the ELISA method. Statistical analysis of the data was performed using IBM SPSS Statistics 29.0 data analysis software. Results: There were no statistically significant results after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity and recurrence of pituitary adenoma and the control groups, the analysis revealed no statistically significant differences between the groups (p > 0.05). For FGFR4 levels: PA patients vs. control group: median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121. Conclusions: While this study did not find statistically significant associations, further research with larger sample sizes, additional genetic markers, and functional studies could provide deeper insights into the role of FGFR4 in PA development.

A 41-year-old primigravida woman transferred from an outside hospital to our Lithuanian University of Health Sciences Hospital with acute-onset severe occipital headache, accompanied by nuchal rigidity, nausea, and vomiting at 35+5 weeks’ gestation. The patient was Hunt and Hess grade I or II with a GCS of 13 and was intubated under sedation and transferred to the NICU. Computed tomography revealed the presence of hemorrhage in the suprasellar, interpeduncular, left cerebellopontine angle, anterior segments of Sylvian cisterns and IV ventricle. Suspicion of a 1.5 mm saccular aneurysm in the distal part of the C7 segment of the left ACI on CTA was ruled out by DSA without evidence of vascular malformations or other structural sources of bleeding. The caesarean section was performed based on the predominant indications observed in the ultrasound assessment. Post-surgery extubated, fully conscious, no focal or generalized neurological deficits, predominantly painful and meningeal syndromes. The transcranial Doppler assessment of mean flow velocity (MFV) in the MCA indicated the presence of bilateral mild vasospasm (MFV of 120-149 cm/s), with no clinical symptoms expressed during the initial fourteen-day period in the NICU. A second diagnostic cerebral angiography, performed thirteen days later, did not reveal any cerebrovascular abnormalities. The choice of diagnostic approach should be tailored on a case-by-case basis, and it is not reasonable to delay or defer necessary emergency maternal diagnosis because of pregnancy in the presence of a suspicious and negative CTA, independently of the extent of hemorrhage.

Aim This study aimed to determine the associations of MEG3 rs7158663, rs4081134 gene variants, as well as the immunohistochemical markers Ki-67, p53, and CK18, with the clinical features of pituitary neuroendocrine tumors (PitNETs).

Methods This case-control study included 340 individuals who were divided into two groups: a control group (n=220) and a PitNETgroup (n=120). DNA was isolated from the venous blood of study participants by the leukocyte salt precipitation method. Real-time polymerase chain reaction was used for the MEG3 rs7158663, rs4081134 single nucleotide variants genotyping. Immunohistochemical analysis of Ki-67 labeling index and p53 protein biomarkers was performed using the automated Ventana BenchMark ULTRA PLUS staining system, following the manufacturer’s recommendations. CK18 immunostaining was conducted with the Dako Omnis staining system, following the manufacturer’s recommendations. Monoclonal antibodies SP6, DO-7, and DC-10 were used to detect Ki-67 labeling index, p53, and CK18, respectively. Statistical data analysis was performed using the “IBM SPSS Statistics 30.0” program.

Results Genotype and allele frequencies of MEG3 rs7158663 and rs4081134 variants showed no significant differences between healthy controls and PitNET patient groups. Additionally, no associations were found between either MEG3 variants and PitNET recurrence, size, invasiveness, and functional status. Ki-67 labeling index (>3% vs. ≤3%) showed no significant differences with any clinical feature of PitNETs (recurrence, size, invasiveness, functional status). In contrast, the p53 H-score was significantly higher in macroadenomas than in microadenomas (median 27 vs. 16; p=0.008). Additionally, invasive pituitary adenomas showed a higher p53 H-score compared with non-invasive tumors (median 27 vs. 20; p=0.018). Negative CK18 immunostaining was significantly more frequent in invasive than non-invasive PitNETs (44.4% vs. 13.3%; p < 0.001) and in non-functioning compared to functioning adenomas (42.0% vs. 18.4%; p=0.011). No significant associations were found between either MEG3 variant and Ki-67 LI, p53 H-score, or CK18 immunohistochemical reactions.

Conclusions This study found that a higher p53 H-score was significantly associated with larger PitNET size and invasiveness. Negative CK18 staining was associated with non-functioning and invasive PitNETs. P53 expression and CK18 status may serve as useful prognostic markers in PitNETs.