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Slide 1 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze
Slide 2 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze
Slide 3 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations
Slide 4 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work
Slide 5 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods
Slide 6 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D
Slide 7 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration
Slide 8 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence
Slide 9 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence
Slide 10 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence
Slide 11 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence
Slide 12 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer
Slide 13 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer.
Slide 14 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells.
Slide 15 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV )
Slide 16 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria.
Slide 17 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation.
Slide 18 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other.
Slide 19 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP).
Slide 20 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH).
Slide 21 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer.
Slide 22 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer.
Slide 23 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer.
Slide 24 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Thus, sharp activation of mitochondrial antioxidant system, (GSH-Px, GR) revealed in BHP with PING(3-4) regions and malignant tumor epithelial cells, indicates to intensification of defensive abilities of tumor cells. (to withstand switching of the mitochondrial way of apoptosis, induced by free radicals).
Slide 25 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Thus, sharp activation of mitochondrial antioxidant system, (GSH-Px, GR) revealed in BHP with PING(3-4) regions and malignant tumor epithelial cells, indicates to intensification of defensive abilities of tumor cells. (to withstand switching of the mitochondrial way of apoptosis, induced by free radicals). Thus, stimulation of the activity of SDH and retention of COX activity in epithelial cells of prostate malignant tissue may be responsible for sharp activation of isocitrate dehydrogenase and correspondingly, for significant accumulation of NADP(H). Laser Induced Fluorescence spectra have shown the incresead intensity of NADP(H) peak in case of malignant tumor tissue that corresponds with investigations in Mitochondria of tumor epithelial cells. Accumulation of NADP(H). may stipulate a sharp activation of the glutathione-depended system, which was proved by our investigations. Activation of the GSH-dependent system (GSH-Px, GR) presumably would be responsible for resistance of cancer cells against the oxidative stress. Changes in the activity of enzymes of the II and IV complexes of mitochondrial respiration chain and antioxidant system, in case of prostate malignant trabsformation, are reflection of specific metabolic changes in mitochondria. All the Above mentioned indicates to resistance of prostate malignant cells and correspondingly, to intensification of proliferation processes. Conclusions:
Slide 26 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Thus, sharp activation of mitochondrial antioxidant system, (GSH-Px, GR) revealed in BHP with PING(3-4) regions and malignant tumor epithelial cells, indicates to intensification of defensive abilities of tumor cells. (to withstand switching of the mitochondrial way of apoptosis, induced by free radicals). Thus, stimulation of the activity of SDH and retention of COX activity in epithelial cells of prostate malignant tissue may be responsible for sharp activation of isocitrate dehydrogenase and correspondingly, for significant accumulation of NADP(H). Laser Induced Fluorescence spectra have shown the incresead intensity of NADP(H) peak in case of malignant tumor tissue that corresponds with investigations in Mitochondria of tumor epithelial cells. Accumulation of NADP(H). may stipulate a sharp activation of the glutathione-depended system, which was proved by our investigations. Activation of the GSH-dependent system (GSH-Px, GR) presumably would be responsible for resistance of cancer cells against the oxidative stress. Changes in the activity of enzymes of the II and IV complexes of mitochondrial respiration chain and antioxidant system, in case of prostate malignant trabsformation, are reflection of specific metabolic changes in mitochondria. All the Above mentioned indicates to resistance of prostate malignant cells and correspondingly, to intensification of proliferation processes. Conclusions: General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP).
Slide 27 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Thus, sharp activation of mitochondrial antioxidant system, (GSH-Px, GR) revealed in BHP with PING(3-4) regions and malignant tumor epithelial cells, indicates to intensification of defensive abilities of tumor cells. (to withstand switching of the mitochondrial way of apoptosis, induced by free radicals). Thus, stimulation of the activity of SDH and retention of COX activity in epithelial cells of prostate malignant tissue may be responsible for sharp activation of isocitrate dehydrogenase and correspondingly, for significant accumulation of NADP(H). Laser Induced Fluorescence spectra have shown the incresead intensity of NADP(H) peak in case of malignant tumor tissue that corresponds with investigations in Mitochondria of tumor epithelial cells. Accumulation of NADP(H). may stipulate a sharp activation of the glutathione-depended system, which was proved by our investigations. Activation of the GSH-dependent system (GSH-Px, GR) presumably would be responsible for resistance of cancer cells against the oxidative stress. Changes in the activity of enzymes of the II and IV complexes of mitochondrial respiration chain and antioxidant system, in case of prostate malignant trabsformation, are reflection of specific metabolic changes in mitochondria. All the Above mentioned indicates to resistance of prostate malignant cells and correspondingly, to intensification of proliferation processes. Conclusions: General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Thank you for attention
Slide 28 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Thus, sharp activation of mitochondrial antioxidant system, (GSH-Px, GR) revealed in BHP with PING(3-4) regions and malignant tumor epithelial cells, indicates to intensification of defensive abilities of tumor cells. (to withstand switching of the mitochondrial way of apoptosis, induced by free radicals). Thus, stimulation of the activity of SDH and retention of COX activity in epithelial cells of prostate malignant tissue may be responsible for sharp activation of isocitrate dehydrogenase and correspondingly, for significant accumulation of NADP(H). Laser Induced Fluorescence spectra have shown the incresead intensity of NADP(H) peak in case of malignant tumor tissue that corresponds with investigations in Mitochondria of tumor epithelial cells. Accumulation of NADP(H). may stipulate a sharp activation of the glutathione-depended system, which was proved by our investigations. Activation of the GSH-dependent system (GSH-Px, GR) presumably would be responsible for resistance of cancer cells against the oxidative stress. Changes in the activity of enzymes of the II and IV complexes of mitochondrial respiration chain and antioxidant system, in case of prostate malignant trabsformation, are reflection of specific metabolic changes in mitochondria. All the Above mentioned indicates to resistance of prostate malignant cells and correspondingly, to intensification of proliferation processes. Conclusions: General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Thank you for attention winamdebare jirkvlis lokalizacia da zonaluri anatomia CZ – centraluri zona; PZ – periferiuli zona; TZ – gardamavali zona prostatis keTilTvisebiani simsivne viTardeba prostatis kranialur nawilSi ZiriTadad periureTraluri jirkvlebidan PIN ubnebiani keTilTvisebiani da avTvisebiani simsivneebi (ukana kaudalur nawilSi) mTavari samozne jirkvlovani epiTeliumis sekretoruli ujredebia prostatis epiTeliumSi arCeven bazalur, sekretorul da parakrinul-endokrinul ujredebs
Slide 29 - Iv. Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences Department of Biology Division of Cellular and Molecular Biology Prostate Cancer Epithelial Cells and The Changes That Take Place During Their Malignant Transformation PhD Student – Liana Ramishvili Scientific supervisor - Prof. N. Kotrikadze Mitochondria Incresed production of Reactive Oxygen Species (ROS) Intensification of Freeradical Processes Mitochondrial Defects Krebs Cycle Functions Properly Malignant transformation of Epithelial Cells of Prostate Increased electons Flow to the Electon transport Chain Increased rate of Mitochondrial DNA Mutations To study the metabolic changes that take place in prostate epithelial cells during their malignant transformation. Tasks: To study of prostate tumor tissue by fluorescence spectroscopy. To study the mitochondrial defects (respiratory chain enzymes and gluthatione dependent system) in epithelial cells of prostate tumor. The Goal of the Work Object of investigation: Tumour tissue of patients with prostate tumours: - Prostate benign hyperplasia; - Prostate benign hyperplasia with PING(3-4) regions; - Prostate Cancer. Method of Investigation: Laser induced Fluorescence Spectroscopic Methods Histo-morphological pictures of Prostate Tumours. A. Controle group B Benign Hyperplasia C. Benign Hyperplasia with PIN regions D. Prostate adenocarcinoma A B C D Laser Canceroscope Consists of 4 blocks : Lights Source block; Sample block Registration block Data collecting and processing block. Excitation was carried out by N2 laser: =337nm wavelength. Recording of Spectra was carried out in the 300- 500 nm wavelength region. Light source Sample Data collection and processing N2 Laser registration The Study of Prostate Tumour tissue by Laser induced Fluorescence Benign tumour Benign tumour with PING(3-4) regions Prostate Cancer The Changes of NADH Fluorescennce peaks intensities tumor tissue of prostate (440-460 nm) 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Conclusion Sharply Increased intensity of the Nicotinamide Coenzymes peak (440-460 nm) in benign prostate tumor with PING3-4 regions and in prostate adenocarcinoma compared with benign tumor tissue spectra, reflects the type of metabolism that is typical to prostate malignant tumor cells. The Study of Mitochondrial respiratory chain enzymes (complex II and Complex IV ) The Activity of Succinatedehydrogenase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The sharp increase in SD activity presumably indicates on the enhanced electrons flow in respiratory chain of mitochondria. 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Cytochromeoxidase The insignificant changes in COX activity presumably indicates on the low level of terminal oxidation. Thus, - Sharp increase of the activity of SDH (complex II); - Insignificant changes of COX (complex IV) activity ; These changes Presumably indicates to activation of Krebs cycle in mitochondria and increase of electrons flow in respiration chain on the one hand, and to impairment of the terminal oxidation of oxygen, on the other. General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Glutathione-dependent Enzymes : Glutathione peroxidase (GSH-Px); Glutathione reductase (GR); Reduced Glutathione (GSH). The Activity of Glutathione Peroxidase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Activity of Glutathione Reductase 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. The Amount of Reduced Glutathione 1- Prostate Benign Hyperplasia; 2- Prostate Benign Hyperplasia with PING3-4 regions; 3- Prostate Cancer. Thus, sharp activation of mitochondrial antioxidant system, (GSH-Px, GR) revealed in BHP with PING(3-4) regions and malignant tumor epithelial cells, indicates to intensification of defensive abilities of tumor cells. (to withstand switching of the mitochondrial way of apoptosis, induced by free radicals). Thus, stimulation of the activity of SDH and retention of COX activity in epithelial cells of prostate malignant tissue may be responsible for sharp activation of isocitrate dehydrogenase and correspondingly, for significant accumulation of NADP(H). Laser Induced Fluorescence spectra have shown the incresead intensity of NADP(H) peak in case of malignant tumor tissue that corresponds with investigations in Mitochondria of tumor epithelial cells. Accumulation of NADP(H). may stipulate a sharp activation of the glutathione-depended system, which was proved by our investigations. Activation of the GSH-dependent system (GSH-Px, GR) presumably would be responsible for resistance of cancer cells against the oxidative stress. Changes in the activity of enzymes of the II and IV complexes of mitochondrial respiration chain and antioxidant system, in case of prostate malignant trabsformation, are reflection of specific metabolic changes in mitochondria. All the Above mentioned indicates to resistance of prostate malignant cells and correspondingly, to intensification of proliferation processes. Conclusions: General scheme of energy metabolism Possible alterations in mitochondria of epithelial cells of prostate malignant tissue (BHP with PIN G3-4,regions, CaP). Thank you for attention winamdebare jirkvlis lokalizacia da zonaluri anatomia CZ – centraluri zona; PZ – periferiuli zona; TZ – gardamavali zona prostatis keTilTvisebiani simsivne viTardeba prostatis kranialur nawilSi ZiriTadad periureTraluri jirkvlebidan PIN ubnebiani keTilTvisebiani da avTvisebiani simsivneebi (ukana kaudalur nawilSi) mTavari samozne jirkvlovani epiTeliumis sekretoruli ujredebia prostatis epiTeliumSi arCeven bazalur, sekretorul da parakrinul-endokrinul ujredebs prostatis keTilTvisebiani hiperplazia prostatis adenokarcinoma