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5 results on '"Simeon Rangelov"'

1. Expression profiling of muscle invasive and non-invasive bladder tumors for biomarkers identification related to drug resistance, sensitivity and tumor progression

Author

Olga Antonova, Blaga Rukova, Boris Mladenov, Simeon Rangelov, Zora Hammoudeh, Desislava Nesheva, Rada Staneva, Viktoria Spasova, Evgeni Grigorov, Savina Hadjidekova, Chavdar Slavov, and Draga Toncheva

Subjects
bladder, cancer, biomarker, muscle-invasive, drug, resistance, Biotechnology, TP248.13-248.65
Abstract

Many bladder cancer (BC) patients with early disease are asymptomatic and diagnosed at advanced stage when the therapeutic options are limited. This necessitates the development of reliable predictive molecular biomarkers that will ensure a positive therapeutic response in every patient. The aim of this study was to screen for alterations in gene expression levels related to drug sensitivity and resistance that may be further explored as potential predictive therapeutic biomarkers. Gene expression analysis of the 168 genes from two panels for Cancer drug resistance and metabolism (PAHS004) and Cancer Drug Targets (PAHS507z) was performed. A total of 47 transitorial cell bladder cancer samples of stage pTa, pT1, pT2 were investigated using the pooling method, which allows reducing the effect of biological variation and detecting only significant expression changes. Differential gene expression was calculated using the ΔΔCt method with GPDH as a housekeeping gene. The 4.0-fold change in gene expression was used as the cut-off threshold to determine upregulation or downregulation compared to normal bladder tissue (negative control). Significance of the differences in the expression profiles was assessed by nonparametric one-way analysis of variance (ANOVA) with Dunn’s multiple comparison tests and Mann-Witney test. We demonstrated a correlation of tumor invasion and several up-regulated genes related to chemotherapy resistance. For the first time, this study demonstrated overexpression of CDK8, CDK9, FIGF, HDAC11, IGF1 and PDGFRA genes in muscle-invasive bladder carcinomas. These genes and their proteins could be used as potential biomarkers for bladder cancer progression or prospective therapeutic targets.

Published
2020
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2. Clinical impact of copy number variation changes in bladder cancer samples

Author

Rada Staneva, Olga Antonova, Zora Hammoudeh, Simeon Rangelov, Dimitar Serbezov, Savina Hadjidekova, Victoria Spasova, Desislava Nesheva, Draga Toncheva, Lubomir Balabanski, Boris Mladenov, Mihail Ganev, Radoslava Vazharova, and C. Slavov

Subjects
Genome instability, Cancer Research, Bladder cancer, Oncogene, Cancer, General Medicine, Articles, Biology, medicine.disease, invasion, Molecular medicine, Metastasis, Loss of heterozygosity, copy number variations, Immunology and Microbiology (miscellaneous), medicine, Cancer research, cancer, metastasis, loss of heterozygosity, Copy-number variation, bladder
Abstract

The aim of the present study was to detect copy number variations (CNVs) related to tumour progression and metastasis of urothelial carcinoma through whole-genome scanning. A total of 30 bladder cancer samples staged from pTa to pT4 were included in the study. DNA was extracted from freshly frozen tissue via standard phenol-chloroform extraction and CNV analysis was performed on two alternative platforms (CytoChip Oligo aCGH, 4x44K and Infinium OncoArray-500K BeadChip; Illumina, Inc.). Data were analysed with BlueFuse Multi software and Karyostudio, respectively. The results highlight the role of genomic imbalances in regions containing genes with metastatic and proliferative potential for tumour invasion. A high level of genomic instability in uroepithelial tumours was observed and a total of 524 aberrations, including 175 losses and 349 gains, were identified. The most prevalent genetic imbalances affected the following regions: 1p, 1q, 2q, 4p, 4q, 5p, 5q, 6p, 6q, 7q, 8q, 9p, 9q, 10p, 10q, 11q, 13q and 17q. High-grade tumours more frequently harboured genomic imbalances (n=227) than low-grade tumours (n=103). A total of 36 CNVs in high-grade bladder tumours were detected in chromosomes 1-5, 8-11, 14, 17, 19 and 20. Furthermore, five loss of heterozygosity variants containing 176 genes were observed in high-grade bladder cancer and may be used as potential targets for precision therapy. Revealing specific chromosomal regions related to the metastatic potential of uroepithelial tumours may lay a foundation for implementing molecular CNV profiling of bladder tumours as part of a routine progression risk estimation strategy, thus expanding the personalized therapeutic approach.

Published
2019

4. Perspectives For Target Therapy In The Treatment Of Malignant Neoplasms Of The Urinary Bladder

Author

Simeon Rangelov, Boris Mladenov, C. Slavov, Draga Toncheva, and Olga Antonova

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine, General Medicine, Target therapy, business
Abstract

Етиологията, патогенезата и лечението на злокачествените новообразувания на пикочния мехур все още пораждат редица въпроси. Установени са биомаркери, показващи разлики в молекулния образ на инвазивния и неинвазивния уроепителен карцином, които са част от факторите, отговорни за големите вариации в лечението дори и при тумори с еднакъв хистологичен резултат. В момента стандартно прилаганата системна терапия включва различни цитотоксични химиотерапевтични схеми и се основава главно на хистологичната оценка и стадирането на тумора. От май 2016 г. за първи път се разреши прилагането на прицелна терапия при лечение на онкологични зболявания на пикочен мехур. Прицелната терапия се използва за спиране на растежа и разпространението на раковите клетки, посредством потискане на активирани сигнални пътища - най-често на фибробластния, епидермалния и ендотелния растежен фактор. Изборът на „правилното` лекарство се базира до голяма степен върху молекулно-генетичната диагноза на тумора и наличие на специфични биомаркери, показващи възможността за прилагане на едно или друго лекарство. През последните години е постигнат значителен напредък в ерата на молекулната диагностика и прицелната терапия, което неминуемо води до удължаване на преживяемостта на онкопоциентите и подобряване качеството им на живот. В тази статия ние разглеждаме потенциалните и съществуващите възможности за приложение на прецизирана терапия при пациенти с уроепителни тумори.

Published
2018

5. Sperm changes in cases with Varicocele

Author

Stefka Ivanova, I. Ilieva, Valentina K. Ormandzhieva, Simeon Rangelov, P. Tzvetkova, and Emilia Petrova

Subjects
Andrology, endocrine system, Multidisciplinary, Abnormal morphology, urogenital system, Vascular disease, Varicocele, medicine, Who criteria, Biology, medicine.disease, Cytoplasmic droplets, Sperm
Abstract

The aim of this study is to determine the percentage of spermatozoa with abnormal morphology in ejaculates of men with Varicocele by morphometric measurements. Cytological and morphometric studies were performed on sperm samples according to the WHO criteria on 329 patients with vascular disease Varicocele and a control group of 20 healthy men. The results showed the highest percentage of spermatozoa with head anomalies (64%), while tail anomalies and cytoplasmic droplets were rarely observed. In conclusion, the results of the present study suggest a narrow dependence between the degree of degenerative changes in the morpho-functional characteristics of spermatozoa.

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