MOLECULAR MARKERS OF THE PROGRESSION OF CONJUNCTIVAL NEOPLASTIC EPITHELIAL LESIONS.

Conjunctival epithelial lesions vary from benign to borderline malignancy to malignant, therefore it is extremely important to detect the molecular markers of the malignant progression of conjunctival intraepithelial lesions. The aim of our study was to analyse the molecular markers of the progression of conjunctival intraepithelial lesions. We have analysed Ki67, PHH3, Bcl2, P53, P63 and CK7 using standard immunohistochemistry.

MOLECULAR CHARACTERISTICS OF THE HETEROGENEITY OF NON-INVASIVE PAPILLARY UROTHELIAL CARCINOMAS AND THE MARKERS OF THEIR RECURRENCE.

Urothelial carcinoma represents the most common type of bladder cancer (>90%) and is the most frequent malignancy of the urinary tract. Most of the urothelial carcinomas are non-invasive at the time of diagnosis, however they are characterised with the risk of recurrence after surgical treatment. The aim of our study was to investigate the characteristics of tumor heterogeneity and markers of its progression in urothelial papillary carcinomas.

TUMOR INFILTRATING LYMPHOCYTES PECULIARITIES IN DIFFERENT HISTOPATHOLOGICAL AND MOLECULAR SUBTYPES OF GASTRIC CARCINOMA.

Gastric carcinoma represents one of the major causes of cancer related mortality worldwide. Recently, immunotherapeutic means gave the new promise for the treatment of gastric carcinoma, although, not all patients benefit from this type of treatment. Tumor infiltrating lymphocytes (TILs) are considered as one of the promising prognostic and predictive biomarkers in solid tumors.

MICROENVIRONMENT ALTERATIONS IN CONJUNCTIVAL NEOPLASTIC LEOSIONS WITH DIFFERENT PROLIFERATION-APOPTOTIC CHARACTERISTICS.

Different studies indicate that tumor infiltrating lymphocytes (TILs) and tumor associated neutrophils (TANs) play an important role during the progression of malignant tumors. We have analysed the distribution of tumor associated neutrophils (TANs) and tumor infiltrating lymphocytes (TILs) in different conjunctival lesions, with different proliferation and apoptotic characteristics. The distribution of TILs and TANs were evaluated in standard haematoxylin and eosin (H&E) stained sections using the digital pathology software QuPathin normal conjunctiva, actinic keratosis, pterigea, conjunctival intraepithelial neoplasias (CoIN1-3) and conjunctival squamous cell carcinoma (CSCC).

HISTOPATHOLOGICAL, PROLIFERATIVE, APOPTOTIC AND HORMONAL CHARACTERISTICS OF VARIOUS TYPES OF LEIOMYOMAS.

Uterine leiomyomas decrease the quality of life by causing significant morbidity among women of reproductive age. Histologically various types of leiomyoma's can be differentiated. We have analysed the histopathological, proliferation, apoptotic and hormonal profile in different types of leiomyomas.

DISTRIBUTION OF STEM CELLS IN DIFFERENT THYROID LESIONS IN PATIENTS OF REPRODUCTIVE, MENOPAUSAL AND POST-MENOPAUSAL AGE.

Different studies indicate that cancer stem cells (CSCs) play an important role in the progression and therapy resistance in different cancer types. The aim of our study was to analyse the distribution of CSCs in different thyroid lesions, in reproductive, menopausal and post-menopausal women. Study included altogether 200 formalin-fixed and paraffin-embedded tissue material, with the diagnosis of NIFTP, Hashimoto's thyroiditis, papillary thyroid carcinoma (PTC) and PTC and Hashimoto's thyroiditis co-occurred cases.

LOSS OF CAS3 AND INCREASE OF BAX EXPRESSION ASSOCIATED WITH PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA.

Apoptosis plays one of the major roles in the progression of human cancers including cervical carcinoma. The aim of our study was to analyse the expression of Cas3, Bax and their correlation with the proliferation index and ER expression status during the progression of cervical intraepithelial neoplasia (CIN). Study included altogether 140 specimens, divided into two major groups, such as: cervical lesions without co-infections and with co-infections.

STEM CELL INDEX IN THE PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA.

Stem cells represent the small subpopulation of healthy and cancerous tissues, which are characterised with increased proliferation and self-renewal properties. From the many different markers of stem cells, we have investigated the stem cell index during the progression of cervical intraepithelial neoplasia (CIN), based on the immunohistochemical expression of CD44 in total of 140 tissue samples from uterine cervix. In addition, we have performed the profound correlation analysis of CD44 with different epithelial-mesenchymal, proliferation, apoptosis and hormonal markers at both protein and mRNA level.

PHENOTYPIC CHARACTERISTICS OF RELAPSED LEIOMYOMA AND SMOOTH MUSCLE TUMORS OF UNCERTAIN MALIGNANCY POTENTIAL IN REPRODUCTIVE WOMEN.

Uterine leiomyoma represents the most common pelvic tumor in females, including numerous histological subtypes, from which smooth muscle tumors of uncertain malignancy potential (STUMP) represents the diagnostic challenge. On the other hand, the study of the relapse risk markers after laparoscopic myomectomy is of high interest. We investigated the molecular phenotype of different types of leiomyoma after hysterectomy or laparoscopic surgery in reproductive and menopausal women.

DISTRIBUTION OF SEX HORMONES AND LYMPHOCYTES IN REPRODUCTIVE WOMAN WITH THYROID PAPILLARY CARCINOMA AND HASHIMOTO'S THYROIDITIS.

The incidence of papillary thyroid carcinoma is characterised with increasing tendency, with unknown reasons. Frequently the co-occurrence of papillary thyroid carcinoma and Hashimoto's thyroiditis has been observed. The aim of our study was to analyse the expression of hormone receptors, lymphocytic infiltration and thyreocyte/lymphocyte proliferation index in thyroid papillary carcinoma and in Hashimoto's thyroiditis.

EVALUATION OF THE RISK OF CERVICAL INTRAEPITHELIAL NEOPLASIA PROGRESSION BASED ON CELL PROLIFERATION INDEX, EPITHELIAL-MESENCHYMAL TRANSITION AND CO-INFECTIONS.

Human papilloma virus (HPV) infection, especially with high risk types, represent the major etiological factor for the development of cervical precancerous and cancerous lesions. However, other factors including cell proliferation index, epithelial-mesenchymal transition and the presence of co-infections might also influence the progression of cervical intraepithelial neoplasia (CIN). The aim of our study was to analyse, the expression of cell proliferation markers and epithelial-mesenchymal transition markers during the progression of cervical intraepithelial neoplasia, in cases with and without co-infections.

THE STUDY OF THE EXPRESSION OF CDH1, KI67, P53 AND HER2 IN DIFFUSE GASTRIC CARCINOMA.

Gastric cancer represents the fifth most common malignancy and third most common cause of cancer deaths worldwide. There are two major types of gastric carcinoma: enteric type and diffuse type. Diffuse type gastric cancer is frequently associated with the mutations in E-cadherin coding gene CDH1.

TLR9 EXPRESSION, LANGERHANS CELL DENSITY AND LYMPHOCYTIC INFILTRATION IN PROGRESSING CERVICAL INTRAEPITHELIAL NEOPLASIA.

Toll like receptors (TLRs), NK cells, Langerhans cells and T cells play an important role in the protection of host organism from human papilloma virus (HPV) infection. The aim of our study was to analyse TLR9 expression, Langerhans cell density and NK cell and Lymphocytic infiltration in the progression of cervical intraepithelial neoplasia (CIN). By using standard immunohistochemistry, we have investigated TLR9, CD1a Langerhans cell marker, CD56 NK cell marker, CD3 general T cell marker, CD4 T helper cell marker and CD8 cytotoxic T cell marker.

EPIGENETIC CHANGES - HISTONE 3 PHOSPHORYLATION - EPITHELIAL OVARIAN TUMORS.

Histone modifications represent one of the types of epigenetic changes. Histones, undergo different types of epigenetic modifications, including the phosphorylation of serine residues. pHH3 antibodies specifically detect histon-3 protein, when phosphorylated at 10th and 28th serine residues.

PHENOTYPIC CHARACTERISTICS OF TROPHOBLASTIC HYPERPLASIA AND MICROENVIRONMENT ALTERATIONS IN CHORIONIC VILLI IN SPONTANEOUS ABORTIONS.

Hydatidiform mole represents the major cause of the molar pregnancy, which is a special cause of spontaneous abortions. We analysed phenotypic characteristics of epithelial hyperplasia and tumor microenvironment alterations in different types of hydatidiform moles. Standard immunohistochemistry was used for the detection of Ki67, Cyclin D1, p53, BCL2, E-cadherin, p63, Vimentin, CD34, CD3, CD4, CD8 and CD68.

PHENOTYPIC CHARACTERISTICS OF CHORIONIC VILLI DURING GESTATIONAL TROPHOBLASTIC DISEASES.

Differential diagnosis of gestational trophoblastic diseases (GTP) using standard micromorphological examination is complicated and less reliable. Therefore, the aim of our study was to investigate the immunohistochemical phenotype of chorionic villi during GTP, as well as in physiological cases. Study included five groups: I group - normal chorionic villi, II group - chorionic villi with hydropic changes, III group - Partial mole, IV group - Complete mole, V group - early Complete mole.

PROLIFERATIVE/STEM CELL INDEX AND PHENOTYPIC CHARACTERISTICS OF PROLIFERATIVE PROCESSES IN ENDOMETRIUM.

The aim of the study was to explore and identify the relationship between endometrial proliferative/stem cell index and phenotypic characteristics under proliferative processes of endometrium using statistical correlation analysis. The study represents a retrospective research. The coded and depersonalized material data from Acad.

SPECIFICITIES OF ENDOMETRIAL PROLIFERATION/STEM CELL INDEX DISTRIBUTION IN ENDOMETRIOID CARCINOMA OF DIFFERENT GRADE OF MALIGNANCY.

Endometrial neoplasia is the most common malignant tumor of female genital system in developed countries. The incidence of endometrial cancer has increased in the last years and despite advances in diagnosis and treatment, the death rates have steadily been increasing over the past 20 years. Therefore aspects of endometrial cancer development, pathogenesis and effective treatment is especially urgent to this day, as much of the risk for endometrial cancer development is influenced by the environment and lifestyle.

Steroids from Helleborus caucasicus reduce cancer cell viability inducing apoptosis and GRP78 down-regulation.

Helleborus caucasicus (Ranunculaceae) is an endemic plant of the Caucasian flora, widely distributed in West Georgia. Biological activities for the extracts of some Helleborus species including H. caucasicus have been reported.

AGE-RELATED SPECIFICITIES OF ENDOMETRIAL PROLIFERATION/STEM CELL INDEX DISTRIBUTION.

Endometrial stem cells take the special place among somatic stem cells of female reproductive system, since their essence and nature still remains unclear - cellular complexity of endometrium, its hormone-dependence and cycling remodeling makes the study of endometrial stem cells exclusively complicated. Consequently, the detection of endometrial stem cells and identification of their location in the complex cellular hierarchy still remains challenging. The aim of our study was to explore the age-related specificities of endometrial proliferative / stem cell index distribution under normal and hyperplasia conditions.

Isolation of a new disaccharide nucleoside from Helleborus caucasicus: structure elucidation and total synthesis of hellecaucaside A and its β-anomer.

Hellecaucaside A, a new disaccharide nucleoside featuring a 2'-O-α-D-ribofuranosyluridine skeleton and a 4-hydroxybenzoyl group at the 5' position, was isolated from the underground part of Helleborus caucasicus. The structure of the compound was elucidated by means of chemical degradation and spectroscopic analyses, such as 1D/2D NMR, chiral-GC, and HRMS. The total synthesis of hellecaucaside A and its β-anomer was accomplished, unequivocally confirming the structure of the natural product.

Advances in the biotechnological glycosylation of valuable flavonoids.

The natural flavonoids, especially their glycosides, are the most abundant polyphenols in foods and have diverse bioactivities. The biotransformation of flavonoid aglycones into their glycosides is vital in flavonoid biosynthesis. The main biological strategies that have been used to achieve flavonoid glycosylation in the laboratory involve metabolic pathway engineering and microbial biotransformation.

Ultraperformance liquid chromatography tandem mass spectrometry determination of cyanogenic glucosides in Trifolium species.

Cyanogenic glucosides were analyzed by ultra-high-performance liquid chromatography combined with mass spectrometry in 88 Trifolium species grown at the same site. On the basis of the occurrence of cyanogenic glucosides and the linamarin/lotaustralin ratio species could be grouped into five clusters. Cluster C1 included 37 species, which did not contain cyanogens.

Caucasicosides E-M, furostanol glycosides from Helleborus caucasicus.

Nine furostanol glycosides, namely caucasicosides E-M, were isolated from the MeOH extract of the leaves of Helleborus caucasicus, along with 11 known compounds including nine furostanol glycosides, a bufadienolide and an ecdysteroid. Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESIMS(n) analyses. The steroidal composition of leaves of H.

Steroidal glycosides from Ruscus ponticus.

A comparative metabolite profiling of the underground parts and leaves of Ruscus ponticus was obtained by an HPLC-ESIMS(n) method, based on high-performance liquid chromatography coupled to electrospray positive ionization multistage ion trap mass spectrometry. The careful study of HPLC-ESIMS(n) fragmentation pattern of each chromatographic peak, in particular the identification of diagnostic product ions, allowed us to get a rapid screening of saponins belonging to different classes, such as dehydrated/or not furostanol, spirostanol and pregnane glycosides, and to promptly highlight similarities and differences between the two plant parts. This approach, followed by isolation and structure elucidation by 1D- and 2D-NMR experiments, led to the identification of eleven saponins from the underground parts, of which two dehydrated furostanol glycosides and one new vespertilin derivative, and nine saponins from R.