Molecular genetic alterations of FHIT and p53 genes in benign and malignant thyroid gland lesions

Several oncogenes and tumor-suppressor genes are involved either as early or late event in thyroid gland carcinogenesis. Human FHIT (fragile histidine triad) gene is highly conserved gene whose loss of function may be important in the development and/or progression of various types of cancer. We undertook this study to analyze FHIT and p53 gene status in different benignant and malignant thyroid tumors. Status of these genes as well as intensity of apoptosis was analyzed in tumor tissues by molecular genetic methods, immunohistochemistry, and FACS-scan analysis. The majority of the malignant thyroid cancers displayed aberrant expression of FHIT gene, concominant with p53 gene inactivation. This is followed by low rate of apoptosis, which may be important in the development and/or progression of thyroid cancer. We found higher incidence of p53 mutation and aberrant processing of FHIT mRNA in malignant tumors (papillary, follicular, medullary and anaplastic carcinomas) and in those tumors with distant metastasis. The growth of p53(-)/FHIT(-) follicular carcinoma of human origin was much faster in nude mice than p53(+)/FHIT(+) follicular carcinoma, and mice had shorter survival rate. Our results show a correlation between aberrant FHIT and p53 expression, low rate of apoptosis, and malignancy. Concomitant aberration of FHIT gene and p53 could be responsible for development of highly malignant types of thyroid cancer and may be considered as a prognostic marker for these tumors.     

Validation of endogenous controls for gene expression studies in peripheral lymphocytes from war veterans with and without PTSD

Background  

Selection of appropriate endogenous control is a critical step in gene expression analysis. The aim of this study was to evaluate expression stability of four frequently used endogenous controls: β-actin, glyceraldehyde-3-phosphate dehydrogenase, β₂-microglobulin and RNA polymerase II polypeptide A in peripheral blood mononuclear cells from war veterans with and without posttraumatic stress disorder (PTSD). The study was designed as to identify suitable reference gene(s) for normalization of gene expression in peripheral blood mononuclear cells in response to war trauma and/or PTSD.     

Small molecule purine and pseudopurine derivatives: synthesis,cytostatic evaluations and investigation of growth inhibitory effect in non-small cell lung cancer A549

Novel halogenated purines and pseudopurines with diverse aryl-substituted 1,2,3-triazoles were prepared. While p-(trifluoromethyl)-substituted 1,2,3-triazole in N-9 alkylated purine and 3-deazapurine was critical for strong albeit unselective activity on pancreatic adenocarcinoma cells CFPAC-1,1-(p-fluorophenyl)-1,2,3-triazole derivative of 7-deazapurine showed selective cytostatic effect on metastatic colon cancer cells SW620. Importantly, 1-(p-chlorophenyl)-1,2,3-triazole-tagged benzimidazole displayed the most pronounced and highly selective inhibitory effect in nM range on non-small cell lung cancer A549. This compound revealed to target molecular processes at the extracellular side and inside the plasma membrane regulated by GPLD1 and growth factor receptors PDGFR and IGF-1R leading to the inhibition of cell proliferation and induction of apoptosis mediated by p38 MAP kinase and NF-κB, respectively. Further optimisation of this compound as to reduce its toxicity in normal cells may lead to the development of novel agent effective against lung cancer.     

Epigenetic changes as prognostic predictors in endometrial carcinomas

Endometrial carcinoma is one of the most frequent gynecological malignancies of the female. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide, and, therefore, the aim of this study was to identify new potential DNA methylation markers for the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n = 31 and n = 39, respectively). We identified specific DNA methylation signature in high-risk endometrial tumors, and potential molecular biomarker genes (TBX2, CHST11, and NID2) associated with unfavorable clinical predictive and prognostic factors.     

Histology of mental and caudal courtship glands in three genera of plethodontid salamanders (Amphibia: Plethodontidae)

Salamanders in the family Plethodontidae exhibit a unique tail‐straddle walk during courtship that can include the use of sexually dimorphic mental and caudal courtship glands. This study presents novel histological and fine structure data on mental glands and caudal courtship glands in Plethodon mississippi, Desmognathus conanti and Eurycea quadridigitata using both light microscopy and scanning electron microscopy. This study represents the first use of scanning electron microscopy to observe these glands. Both mental and caudal courtship glands were observed to vary seasonally in gland diameter and histology according to the breeding season of each species. Morphological variation was observed across the three species studied in both clustering and relative size of the glands compared to neighbouring mucous and granular glands. Hypertrophied mental glands are larger than mucous or granular glands in all species, but relationships among caudal courtship glands and other skin glands vary among species. In E. quadridigitata, active caudal courtship glands are larger than mucous and granular glands, but in D. conanti, caudal courtship glands are similar in size to granular glands and larger than mucous glands. In P. mississippi, caudal courtship glands are scattered among significantly larger granular glands and are similar in size to mucous glands.     

Diet composition of Belone belone (Linnaeus, 1761) (Pisces: Belonidae) in the Aegean Sea

The objective of this study was to determine the monthly dietary pattern in migratory garfish and to improve our understanding in the seasonality of prey choice. Gut contents of 597 Belone belone specimens collected from the eastern Aegean Sea (Turkey) were analyzed: 79.2% contained food in their guts and 20.8% had empty guts. Crustaceans (36.7%) were the most important prey with a 36.7 index of relative importance (%IRI). Especially brachyurans (13.0%) and copepods played a major role (10.1%), followed by teleosts (26.1%) and other food categories (23.3%) (much of which was of terrestrial origin, including insects). Nannocalanus minor, Clausocalanus arcuicornis, Temora stylifera, Labidocera wollastoni and Oncea media were important copepods found in the guts of B. belone specimens. Analysis of variance of the monthly weight data indicated no significant seasonal differences, except for January and February.     

Correlation of anaemia and cognitive functions measured by the complex reactiometer Drenovac

Cognitive impairment impinges significantly on the quality of life. Previous research revealed that anaemia can have a major influence on cognitive functioningt. The article is a correlational study examining the relationship between anaemia levels and cognitive functioning in adult patients. Sixty-one patients (both inpatients and outpatients), among them 30 anemic and 31 non-anaemic, 33 female and 28 male, aged 32-60 (median 43) treated at the Dept. of Hematology, Clinical Hospital Center Rijeka, Croatia were analysed according to hemoglobin (Hb) level and cognitive ability. Assessment of cognition (convergent inductive thinking) was performed by the Complex reactiometer Drenovac (CRD). The results showed that anaemia significantly undermines cognitive functions in adult patients (p < 0.01). Even in non-anaemic patients (Hb higher than 120 g/L), Hb level is related to better cognitive ability.