Biljana Djordjevic

Ovarian Epithelial Cancer Stem Cells

The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance.

Expression of CD34 in cirrhotic liver--reliance to dedifferentiation.

BACKGROUND/AIM The vascular supply of dysplastic nodules (DN) is altered compared with surrounding cirrhotic nodules. Dysplastic nodules contain unpaired arteries which are isolated arteries unaccompained by bille ducts. In adition, capillarization or neovascularization is evident on CD34 and CD31 staining. The investigation of angiogenic profile of regenerative, dysplastic and nodules of hepatocellular carcinoma aimed at assessing whether vascular profile is in reliance to the process of dedifferentiation of hepatocytes during the course of cirrhosis. METHODS Thirty four liver nodules from surgical biopsies of 12 patients previously undiagnosed to have cirrhosis, were classified as regenerative, dysplastic and small hepatocellular carcinomas (HCC). The investigation included 8 large regenerative nodules (LRN), 11 low grade dysplastic nodules (LGDN), 12 high grade dysplastic nodules (HGDN) and 3 early HCC. Serial sections of the nodules and surrounding cirrhotic liver tissue were immunostained against CD34. The vascular counting method was performed. The results were analysed using SPSS computer statistical program. RESULTS The number of capillary unites showed significant differences among nodular types, with the largest number of capillaries in hepatocellular carcinoma as well as strong reliance to dedifferentiation. CONCLUSION There is a significant correlation of sinusoidal capillarization to dediferentiation of the liver tissue during the course of cirrhosis. From diagnostic view, capillary counting may be helpful to distinguish dysplastic from nondysplastic nodules. The appearance of dysplastic nodules in nonselected surgical biopsies is frequent enough to challenge caution during the follow-up of cirrhotic patients.

Divergent Squamous Differentiation in Upper Urothelial Carcinoma—Comparative Clinicopathological and Molecular Study

Upper urothelial carcinoma (UUC) has a plasticity to demonstrate divergent differentiation with squamous metaplastic elements. There was no previous study exploring profiling of molecular markers in metaplastic squamous upper urothelial carcinoma (SUUC) and conventional upper urothelial carcinoma (CUUC). The aims of this study was to compare expression of the phenotypic characteristics of tumors and molecular markers (p53, p16, cyclin D1, E-cadherin, HER-2, Ki-67, Bcl-2, Bax) in SUUC and CUUC. SUUC was detected in 20% of 44 patients. There was significant difference between SUUC and CUUC in the pathological stage, grade, growth and presence of lymphovasular invasion (p < 0.05; 0.05; 0.05; 0.01 respectively). The mean Ki-67 and p53 labeling index was significantly higher in SUUC than in CUUC (p < 0.05; 0.05). There was no significant difference in the expression of p16, cyclin D1, E-cadherin, HER-2, Bcl-2 and Bax between SUUC and CUUC. Univariant model showed that SUUC was significantly associated with lymphovascular invasion (p = 0.007), Ki-67 activity (p = 0.016) and growth (p = 0.026). Exploration of UUC with squamous divergent differentiation showed changes in phenotypic characteristics and Ki-67, as well as similar molecular profile with CUUC.

Anxiety levels related to the type of therapy for cervical cancer

The aim of this study was to examine the effect of treatment type on anxiety in patients with cervical cancer. Subjects and methods: This prospective study was conducted in 60 patients with cervical cancer treated by radiotherapy. The study was done before treatment, and 3 and 6 months after initial testing. For assessment of anxiety the Hamilton Anxiety Scale (HAM-A) was used.: At baseline, the values of the scale of anxiety in patients who were treated surgically were significantly higher than in patients who had been treated by radiotherapy, but the intensity of anxiety gradually decreased in both groups. In this study, pain and irregular menstrual bleeding were the most important risk factors for the development of anxiety.: Routine assessment should be introduced in clinical practice for the detection and monitoring of anxiety in all patients with cervical cancer, and a psychiatrist should be included in the multidisciplinary team for their treatment.