changes in protein profiles in bortezomib applied multiple myeloma ...

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We approve the thesis of Taylan TURAN ________________________________ Assist. Prof. Dr. Gülşah ŞANLI-MOHAMED Supervisor _______________________________ Assoc. Prof. Dr. Yusuf BARAN Co-Supervisor _______________________________ Prof. Dr. Leman TARHAN Committee Member __________________________________ Prof. Dr. Güray SAYDAM Committee Member _______________________________ Assist. Prof. Dr. Çağlar KARAKAYA Committee Member 26 December 2011 _____________________________ __________________________ Prof. Dr. Durmuş ÖZDEMİR Prof. Dr. R. Tuğrul SENGER Head of the Department of Chemistry Dean of the Graduate School of Engineering and Sciences
ACKNOWLEDGEMENTS First of all, with all my sincerity, I would like to express my deepest gratitude and endless thanks to my supervisor Assist. Prof. Dr. GülĢah ġANLI for giving me the opportunity to take the first step to begin my academic career. From the beginning of my academic life, her incomparable guidance, understanding, encouragement, confidence and everlasting support both have maximized my motivation and have helped me to carry out this project by keeping warm the love of science in my heart. It is a big honour to work with such a wonderful person. I would like to thanks to my co-supervisor Assoc. Prof. Dr. Yusuf BARAN for his useful thoughts, valuable comments, inspiring suggestions and generous helps during my thesis study. I am also thankful to him for opening me to his laboratuary and providing me all the essential facilities to complete my master’s degree. I would especially like to thanks to Prof. Dr. Leman TARHAN for her inspiration, motivation and encouragement. Whenever I give away to despair, she is the first who gives me courage. Furthermore, she is always by my side with her experience whenever I need her. I am extremely lucky and very happy to have a mentor like her. During my first academic experience, many people have assisted me that I feel the need of my appreciations. I am grateful to Cancer Genetics Research Laboratory members, Mass Spectrometry and Proteomic Laboratory members and Biotechnology and Bioengineering Research Center specialists, especially Dane RUSÇUKLU for their kindly helps. Next, I am also thankful to my close friends Murat ÇOLAK, Hüseyin ĠLGÜ, ÇağdaĢ GÖKTAġ and Mehmet Ġlyas COġACAK for their good friendship and constructive comments. Moreover, I owe the rest of my friends working in the Biological Chemistry Laboratory a great debt of gratitude. My special thanks are for Hande BÜYÜKKEBABÇI. Her undeniable supports, care and also endless love are mainly the best motivation for me during my studies. I would never able to succeed to my job without her. Last but not least, I am greatly indepted to my family for their infinite encouragement, constant motivation, enormous patience and limitless love. Numerous thanks to my family. I owe all my success to you. I am in safe with your love!
Page 1: CHANGES IN PROTEIN PROFILES IN BORT
Page 5 and 6: ÖZET BORTEZOMĠB UYGULANAN MULTĠP
Page 7 and 8: 2.1.4.1.2. Two-Dimensional Gel Elec
Page 9 and 10: LIST OF FIGURES Figure Page Figure
Page 11 and 12: LIST OF TABLES Table Page Table 1.1
Page 13 and 14: When normal cells in the body begin
Page 15 and 16: Figure 1.2. Development of Cancer S
Page 17 and 18: the myeloma cells does not help fig
Page 19 and 20: A rare form of MM called Nonsecreto
Page 21 and 22: 1.2.3. Risk Factors for MM A risk f
Page 23 and 24: of the mineralizations by adjusting
Page 25 and 26: To measure the levels of red cells,
Page 27 and 28: The levels of blood urea nitrogen (
Page 29 and 30: By using the system introduced by D
Page 31 and 32: 1.2.7.2. Biology of The Proteasome
Page 33 and 34: Figure 1.10. Ubiquitin-Proteasome P
Page 35 and 36: Figure 1.12. Effect of Bortezomib o
Page 37 and 38: encompasses the investigation of pr
Page 39 and 40: of modification. Ubiquitin is a sma
Page 41 and 42: the given cells. On the other hand,
Page 43 and 44: is-acrylamide (N,N'-methylene-bisac
Page 45 and 46: 2.1.4.2. Detection of Protein Spots
Page 47 and 48: ange of 600-2500 Da. This is the id
Page 49 and 50: ions resolved by the mass analyzer
Page 51 and 52: 2.1.4.5.2. Mass Analyzers Figure 2.
Page 53 and 54:
There is no doubt that different ma
Page 55 and 56:
mask low-quantity proteins that may
Page 57 and 58:
3.1. Materials 3.1.1. Medias CHAPTE
Page 59 and 60:
3.2.5. Cell Proliferation Assay Ant
Page 61 and 62:
After 72 hour incubation period at
Page 63 and 64:
eceptors of the Tumor Necrosis Fact
Page 65 and 66:
The preparation of stock BSA Standa
Page 67 and 68:
3.2.6.3. Detection of the Loss of M
Page 69 and 70:
centrifugation, the supernatant was
Page 71 and 72:
selected symmetrically to load the
Page 73 and 74:
approximately 35 ml, the volume of
Page 75 and 76:
After electrophoresis was finished,
Page 77 and 78:
7 Day Two: Reduction, Alkylation, a
Page 79 and 80:
CHAPTER 4 RESULTS AND DISCUSSION 4.
Page 81 and 82:
% Changes in Cytoplasmic/Mitochondr
Page 83 and 84:
Table 4.1. Magnified Segments of Di
Page 85 and 86:
Table 4.1. Magnified Segments of Di
Page 87 and 88:
After labeling, black and red color
Page 89 and 90:
78 7 8 Y2S Y3S Table 4.2. Results o
Page 91 and 92:
80 12 S4Ca Table 4.2. Results of Di
Page 93 and 94:
82 27 Y5S Table 4.2. Results of Dif
Page 95 and 96:
Spot 4, Ubiquitin-conjugating enzym
Page 97 and 98:
is a transcriptional repressor, but
Page 99 and 100:
activity and loss of mitochondrial
Page 101 and 102:
distributed, but correlate with nat
Page 103 and 104:
DeMartino, G. N. and Slaughter, C.
Page 105 and 106:
proteomic analyses of a systematica
Page 107 and 108:
Mahindraa, A., Hideshimab, T. and A
Page 109 and 110:
Richardson, P. G., Hideshima, T. an
Page 111 and 112:
Terpos, E. 2008. Bortezomib Directl
Page 113 and 114:
A.1. RPMI-1640 Growth Medium APPEND
Page 115 and 116:
Table B.1. Chemicals and Reagents U
Page 117 and 118:
B.4.3. Standard Curve for BSA Table
Page 119 and 120:
Urea (8M) 4.8 g CHAPS (%2) 0.2 g DT
Page 121 and 122:
E. F. G. STOCK REAGENT PREPARATION
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