Review of Hallmarks of Prostate Cancer (PCa) Nilgoon Zarei* Keywords: Prostate Cancer (PCa), Hallmarks of Cancer
|
|
- Laura Regina Henry
- 5 years ago
- Views:
Transcription
1 Article Health Professional Student Journal (1) Review of Hallmarks of Prostate Cancer (PCa) Nilgoon Zarei* Abstract: Prostate cancer (PCa) is the most frequently diagnosed noncutaneous malignancy in men and is the second and third leading cause of cancer mortality for American and Canadian men, respectively 1, 2. PCa is a disease of disrupted prostate cell genomes and corresponding proteins. Cancer progression starting from normal prostate epithelium to androgen- dependent and eventually hormonerefractory carcinoma is very complex and involves multiple processes associated with up/down regulation (malfunction) of different pathways (cell regulatory circuits) 3. PCa, like any other cancer, has stages from I to IV (I corresponds with low-grade benign cancer and IV is an advanced malignant tumor).to determine the PCa stages, the Gleason system is being used, which is solely based on cancer architectural pattern 4. In this study, the ten hallmarks of PCa have been reviewed. It is important to highlight that PCas with low grade Gleason degree usually do not express all the hallmarks presented herein and there is debate regarding considering them cancer or not 4. Keywords: Prostate Cancer (PCa), Hallmarks of Cancer Introduction The mechanisms and proteins involved in cancer development are complex, and multiple of protein signaling pathways should disrupt so that a normal cell develop into cancer. Despite the complexity, these pathways are categorized into ten hallmarks, each representing a different type of breach in a cell s anti-cancer mechanism 5-6. Although there are numerous studies on each hallmark involved with PCa, there is no well-organized literature summarizing all PCa hallmarks. In this paper, a short review on PCa hallmarks is presented. * Interdisciplinary Oncology, Faculty of Medicine, UBC, Canada (nilgoon.zarei@gmail.com) 1. Self-sufficiency in growth signals Cancer cells generate their own growth signals to stimulate mitosis 5-6 The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor which involves with cell growth regulation, differentiation, motility, and adhesion through interaction with different ligands such as EGF. As a result of these interactions, different downstream signaling pathways will be activated, as shown in Figure 1. RAS-MAPK-MEK- ERK * and PI3K-AKT * pathways are activated through EGFR, which both are responsible for tumor-progression. Impaired endocytic down-regulation of
2 EGFR will result in uncontrolled signaling and eventually development into cancer 7.The EGF binding onto the androgen-independent prostatic carcinoma cell line PC3 is analyzed with Scatchard plot, as shown in Fig2. The steep slope of the line in bound/free plot of Fig.2 shows very high affinity between the ligand and receptor (EGF and EGFR). The PC3 solution was being used for two less aggressive PCa cell lines (human prostate carcinoma, LnCap, and classical prostate cancer cell lines, DU 145). This solution increased cell proliferation for both cell lines 8, as shown in Fig 3. Fig 3. Effect of PC3 condition medium on DU145 and LNCab 8. RAS: Rat sarcoma MAPK: Mitogen-Activated Protein Kinases MEK: Mitogen-Activated Protein Kinase Kinase ERK: Extracellular-Signal-Regulated Kinases PI3K: Phosphoinositide 3-Kinase Fig.1. Different signaling pathways, ERk and Akt two important ones in PCa 4 Fig. 2. Scatchard Plot of EGF binding onto PC3 cells, K d = 5.38 nm (very high affinity), Bound/Free(B/F) Insensitivity to anti-growth signals Cancer cells become insensitive to the signals that tell them to stop growing 5-6 Cyclin-Dependent Kinase, Cdks, governs progression through the cell cycle. In cell cycle the transition from G1 to S is governed by the D-type cyclins 9. In response to anti-growth signals; cell might enter a post-mitotic state where they stop going through all the processes of cell division and can no longer proliferate. Cyclin D2, is a cell cycle-regulatory gene whose abnormal expression will force the cells to go through unnecessary replication cycles. This gene is shown to be silent in PCa cells. Analysis of 101 PCa samples showed methylation frequency of Cyclin D2 promoter is significantly high in PCas (32% for PCa vs 6% for nonmalignant prostate tissue) 9, Fig.4. 2
3 Health Professional Student Journal (1) Fig.4 MSP of Cyclin D2 (276 bp) in prostatic tumors and nonmalignant tissues. N/T (nonmalignant/tumors); T3 T10, prostate tumor samples; L and NC negative control; negative control and P, positive control. P16 (151 bp) control Evading Immune Destruction Eliminating the monitoring capability of immune system 6 Cells and tissues are constantly under the control of immune system. This supervision and observation system will aggressively target cancer cells and eliminate them at early stages, however, few of cancer bodies manage to either win this battle or hide from the immune system, in other words evading eradication 6. One way of doing so is by turning off the T cell switch. Cytotoxic T-Lymphocyte- Associated protein 4(CTLA-4), is a protein on the surface of T cells and acts as an off switch for T cells. In PCa, it is shown that blocking CTLA-4 will significantly help to shrink tumors Limitless replication potential Long DNA ends cancer cells have limitless replication potential 5-6 To protect the genome, an enzyme called telomerase adds extra base pairs at the ends of the chromosomes and lengthens the DNA. Telomerase is active during embryogenesis and in cells that need to undergo many cell division cycles, such as stem cells in the bone marrow, but is inactive in adult cells. Therefore, chromosomal DNA becomes shorter with each successive cell division cycle, which sets a limit on the number of cell divisions a cell can undergo. The human telomerase (such as HumanTelomerase Reverse Transcriptase, htert) is regulated by Androgen Receptor (AR) signaling. LNCaP which expresses a mutant but functional AR, meditates telomerase activity and increase transcription Tumor promoting inflammation Cancer initiation/progression via inflammation 6 Inflammation has a profound effect on cancer development (initiation to metastasis). It is believed that inflammation stimulates carcinogenesis 12. Inflammation causes cell/genomic damage, enhances cell replication, and carries many more destructive effects 12. There is a strong relationship between inflammation and PCas 13. The level of proinflammaorty cytokines is shown to be significantly higher in chronic prostatitis sections comparing to normal samples. Moreover, there exists evidence confirming the higher risk of PCa for men with prostatic inflammation history 13.
4 6. Tissue invasion and metastasis Cancer cells invade neighboring cells and spread throughout the body to new sites 5 Spread of cancer cells to other distant tissues and starting new colonies is known as cancer invasion or metastasis. Cancer cells release protease enzyme which allows them to dissociate, and migrate independently in the extracellular space and eventually reside in distant locations and form colonies 14. Interaction between the stromal cellderived factor 1 (SDF-1), known as C-X-C motif Chemokine 12 (CXCL12), and C-X- C Chemokine Receptor type 4 (CXCR-4), also known as fusin, plays a critical role in PCa metastasis into the bone. The expression of CXCL4 is shown in both PCa and bone stromal cells. In fact migration and culturing of PC-3 cells in bone depends on CXCL12/CXCR4 signaling and Akt activation through PI3- kinase 14, as shown in Fig1. Also CXCL12 induces expression of Matrix Metallo Peptidase 9 (MMP-9) in PCa cells, which is associated with tumor progression and metastasis. 7. Sustained angiogenesis The growth of new blood vessels 5 Cancerous bodies which reach a size of 1 mm need to initiate angiogenesis, to receive oxygen and nutrients from the vessels. So they turn on the angiogenic switch and start to secrete angiogenesisinducing factors. One such important factor is Vascular Endothelial Growth Factor (VEGF) which is mediated by hypoxia, cytokines and androgen 5, 15. VEGF also involves in other pathways such as (Ras, Raf, and Src ** ) activation and inactivation of genes responsible for tumor suppression 15. VEGF levels, measured by immunohistochemical analysis showed higher level of VEGF in patients with metastatic prostatic cancer than those with localized prostatic cancer Genome Instability DNA mutation and repair 6 Certain genome alteration during mutation can simply enforce the normal cells to outgrow and develop into cancer. Poly (ADP-ribose) Polymerase, PARP, is a protein involved in repairing DNA damage of cancerous cell (the natural damage during fast replication and the artificial damage during cancer treatment) 16. PCa of patients which lacks the homologous recombination DNA repair (due to loss-of-function BRCA1 * or BRCA2 * mutations) can be treated with PARP inhibitors. PARP also impacts ERG transcription and androgen signaling which are very important pathways in PCas 16. * BRCA1: the official name of this gene is breast cancer 1, early onset. * BRCA2: the official name of this gene is breast cancer 2, early onset. ** RAS: Rat sarcoma, RAF:Rapidly Accelerated Fibrosarcoma, SRC: Steroid Receptor Coactivator, 4
5 Health Professional Student Journal (1) 9. Evading apoptosis Cancer cells resist apoptosis 5 All healthy cells will go through natural (programmed) cell death process known as apoptosis. Apoptosis can be triggered from both internal and external signals. Defender Against Cell Death 1, DAD1, is a downstream target of the NFkB(Nuclear Factor Kappa-Light-Chain- Enhancer of activated B cells) survival pathway and boosts cell resistance to apoptosis. High DAD1 expression is associated with cancerous epithelium and its protein level also exhibited a strong association with microscopic tumor architecture (Gleason pattern) Deregulating cellular energetics Reprogrammed metabolism to support proliferation 6 Cancer cells reprogram glucose metabolism, which increases the uptake of glucose into the cell and also favor glycolysis even under aerobic condition. Pyruvate kinase M2 (PKM2) is essential for aerobic glycolysis. By immunohistochemistry the researchers have shown that the expression level of PKM2 is higher in aggressive prostate tumor 18. Conclusion In this survey, ten hallmarks of PCa have been reviewed and summarized. As explained in this paper, interruption in cells regulatory mechanisms can eventually result in modified biological capabilities (hallmarks) and cell development into tumor. Any prostate lesion should adopt all the aforementioned hallmarks of cancer in order to be considered cancerous. References 1. Canadian Cancer Society: Canadian Cancer Statistics. (2012). 2. American Cancer Society. Cancer Facts & Figures. (2013). 3. Tindall, D. ( 2013). Prostate Cancer Biochemistry, Molecular Biology and Genetics, Springer New York, ISBN , Huang, Y. et al. (2010). Epidermal Growth Factor Receptor (EGFR). Phosphorylation, Signaling and Trafficking in Prostate Cancer. Oncogene 29, ; doi: /onc Hanahan, D., Weinberg, R. A., & Francisco, S. (2000). The Hallmarks of Cancer Review University of California at San Francisco, 100, Hanahan, D., & Weinberg, R. a. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), doi: /j.cell Balducci J. et al.(2010) Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells, Oncogene p4947.doi: 038/onc Hofer, D. R, et al. (1991). Autonomous Growth of Androgen-independent Human Prostatic Carcinoma Cells : Role of Transforming Growth Factor α Autonomous Growth of Androgen-independent Role of Transforming Growth Factor a1,
6 9. Padar, A., et al.(2003). Inactivation of Cyclin D2 Gene in Prostate Cancers by Aberrant Promoter Methylation, Klyushnenkova, E. N., et al. (2014). Breaking immune tolerance by targeting CD25+ regulatory T cells is essential for the anti-tumor effect of the CTLA-4 blockade in an HLA-DR transgenic mouse model of prostate cancer. The Prostate, 74(14), doi: /pros Hendriksen, P. J. M., et al. (2006). Evolution of the androgen receptor pathway during progression of prostate cancer. Cancer research, 66(10), doi: / can Grivennikov, S. et al. (2010). Immunity, Inflammation, and Cancer, Cell, 140(6) Dal Moro, F., et al. (2013). Inflammation and prostate cancer. Urologic oncology, 31(5), 712. doi: /j.urolonc Cxcl, M. et al. (2006). CXCL12 / CXCR4 Signaling Activates Akt-1and MMP-9 Expression in Prostate Cancer Cells : The Role of Bone, 48(April 2005), doi: /pros Russo, G., et al. (2012). Angiogenesis in prostate cancer: onset, progression and imaging. BJU international, 110(11 Pt C), E doi: /j x x 16. Pusceddu, S. et al. (2013). Pancreatic welldifferentiated neuroendocrine neoplasms (pwdnens): what place for everolimus and sunitinib derived from ESMO clinical practice guidelines in the therapeutic algorithm? Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 24(5), doi: /annonc/mdt Jung, K. (2007). A molecular correlate to the Gleason grading system for prostate adenocarcinoma. European urology, 51(3), Retrieved from Wong N, et al. (2014). Changes in PKM2 associate with prostate cancer progression, Cancer invest, 32(7): doi: /
Transformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture:
Transformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture: Spandana Baruah December, 2016 Cancer is defined as: «A disease caused
More informationDeregulation of signal transduction and cell cycle in Cancer
Deregulation of signal transduction and cell cycle in Cancer Tuangporn Suthiphongchai, Ph.D. Department of Biochemistry Faculty of Science, Mahidol University Email: tuangporn.sut@mahidol.ac.th Room Pr324
More informationThe Hallmarks of Cancer
The Hallmarks of Cancer Theresa L. Hodin, Ph.D. Clinical Research Services Theresa.Hodin@RoswellPark.org Hippocrates Cancer surgery, circa 1689 Cancer Surgery Today 1971: Nixon declares War on Cancer
More informationIntroduction. Cancer Biology. Tumor-suppressor genes. Proto-oncogenes. DNA stability genes. Mechanisms of carcinogenesis.
Cancer Biology Chapter 18 Eric J. Hall., Amato Giaccia, Radiobiology for the Radiologist Introduction Tissue homeostasis depends on the regulated cell division and self-elimination (programmed cell death)
More informationBiochemistry of Carcinogenesis. Lecture # 35 Alexander N. Koval
Biochemistry of Carcinogenesis Lecture # 35 Alexander N. Koval What is Cancer? The term "cancer" refers to a group of diseases in which cells grow and spread unrestrained throughout the body. It is difficult
More informationBasic tumor nomenclature
Jonas Nilsson jonas.a.nilsson@surgery.gu.se Sahlgrenska Cancer Center Bilder gjorda av Per Holmfeldt och Jonas Nilsson Benign tumor Basic tumor nomenclature Malignant tumor = cancer Metastasis Carcinoma:
More informationnumber Done by Corrected by Doctor Maha Shomaf
number 19 Done by Waseem Abo-Obeida Corrected by Abdullah Zreiqat Doctor Maha Shomaf Carcinogenesis: the molecular basis of cancer. Non-lethal genetic damage lies at the heart of carcinogenesis and leads
More informationCancer and Oncogenes Bioscience in the 21 st Century. Linda Lowe-Krentz
Cancer and Oncogenes Bioscience in the 21 st Century Linda Lowe-Krentz December 1, 2010 Just a Few Numbers Becoming Cancer Genetic Defects Drugs Our friends and family 25 More mutations as 20 you get older
More informationCELL BIOLOGY - CLUTCH CH CANCER.
!! www.clutchprep.com CONCEPT: OVERVIEW OF CANCER Cancer is a disease which is primarily caused from misregulated cell division, which form There are two types of tumors - Benign tumors remain confined
More informationBIT 120. Copy of Cancer/HIV Lecture
BIT 120 Copy of Cancer/HIV Lecture Cancer DEFINITION Any abnormal growth of cells that has malignant potential i.e.. Leukemia Uncontrolled mitosis in WBC Genetic disease caused by an accumulation of mutations
More informationChapt 15: Molecular Genetics of Cell Cycle and Cancer
Chapt 15: Molecular Genetics of Cell Cycle and Cancer Student Learning Outcomes: Describe the cell cycle: steps taken by a cell to duplicate itself = cell division; Interphase (G1, S and G2), Mitosis.
More informationCancer Genetics. What is Cancer? Cancer Classification. Medical Genetics. Uncontrolled growth of cells. Not all tumors are cancerous
Session8 Medical Genetics Cancer Genetics J avad Jamshidi F a s a U n i v e r s i t y o f M e d i c a l S c i e n c e s, N o v e m b e r 2 0 1 7 What is Cancer? Uncontrolled growth of cells Not all tumors
More informationGenetics and Cancer Ch 20
Genetics and Cancer Ch 20 Cancer is genetic Hereditary cancers Predisposition genes Ex. some forms of colon cancer Sporadic cancers ~90% of cancers Descendants of cancerous cells all cancerous (clonal)
More informationCancer Cell Self Sufficiency in Growth Signals
Name Date Cancer Cell Self Sufficiency in Growth Signals Part 1: Introduction Read the introduction. Draw a flower in the box when finished with this step. RAS Diagram Use the space below the diagram to
More informationVIII Curso Internacional del PIRRECV. Some molecular mechanisms of cancer
VIII Curso Internacional del PIRRECV Some molecular mechanisms of cancer Laboratorio de Comunicaciones Celulares, Centro FONDAP Estudios Moleculares de la Celula (CEMC), ICBM, Facultad de Medicina, Universidad
More informationOncolytic Virotherapy: Targeting Cancer Stem Cells
Oncolytic Virotherapy: Targeting Cancer Stem Cells Cancer Stem Cells (CSCs) or Cancer Initiating Cells (CICs) A consensus of five defining criteria has been established to affirm the existence of CICs:
More informationDiabetes Mellitus and Breast Cancer
Masur K, Thévenod F, Zänker KS (eds): Diabetes and Cancer. Epidemiological Evidence and Molecular Links. Front Diabetes. Basel, Karger, 2008, vol 19, pp 97 113 Diabetes Mellitus and Breast Cancer Ido Wolf
More information1. The metastatic cascade. 3. Pathologic features of metastasis. 4. Therapeutic ramifications. Which malignant cells will metastasize?
1. The metastatic cascade 3. Pathologic features of metastasis 4. Therapeutic ramifications Sir James Paget (1814-1899) British Surgeon/ Pathologist Paget s disease of Paget s disease of the nipple (intraductal
More informationPart I. An Introduction to Cancer
Part I An Introduction to Cancer 2 Chapter 1 Cancer: Descriptive Overview Cancer is a disease in which cells propagate uncontrollably. These cells can come from many different parts of the body and the
More informationEarly Embryonic Development
Early Embryonic Development Maternal effect gene products set the stage by controlling the expression of the first embryonic genes. 1. Transcription factors 2. Receptors 3. Regulatory proteins Maternal
More informationUNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA PhD SCHOOL. PhD THESIS
UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA PhD SCHOOL PhD THESIS THE IMPORTANCE OF TUMOR ANGIOGENESIS IN CEREBRAL TUMOR DIAGNOSIS AND THERAPY ABSTRACT PhD COORDINATOR: Prof. univ. dr. DRICU Anica PhD
More informationConvergent and Divergent Mechanisms in Aging and Cancer
Convergent and Divergent Mechanisms in Aging and Cancer Mariana S. De Lorenzo, PhD Department of Cell Biology & Molecular Medicine delorems@umdnj.edu LEARNING OBJECTIVES 1. To identify convergent and divergent
More informationC) The graph should look exactly like the graph on the left (Mut1 cells + Mating Pheromone for 3 hours at 25 degrees). The cells arrest in G1.
706-2000-Exam 4 Answer Key 1) The question asks you to explain peaks A and B in the top graph. The other two graphs were there to give you hints. The question did not ask for these other two graphs to
More informationBiologics Effects of Targeted Therapeutics
Report on the isbtc Mini-symposium on Biologics Effects of Targeted Therapeutics Michael B. Atkins, MD Beth Israel Deaconess Medical Center Louis Weiner, M.D. Fox Chase Cancer Center Report on the isbtc
More informationActive surveillance: Shrinking the grey zone. Sommerakademi e Munich, June rd FOIUS Tel Aviv, July 2016
Active surveillance: Shrinking the grey zone Active surveillance: 3 rd FOIUS Tel Aviv, July 2016 Shrinking the grey zone Sommerakademi e Munich, June 30 2016 Active Surveillance for low risk PCa What has
More informationCRYOSENSITIZERS: Ablation at the Edge
CRYOSENSITIZERS: Ablation at the Edge John G. Baust Institute of Biomedical Technology State University of New York Binghamton, NY USA JGBaust@binghamton.edu Precision targeting Challenge Uncertain margin
More information1.The metastatic cascade. 2.Pathologic features of metastasis. 3.Therapeutic ramifications
Metastasis 1.The metastatic cascade 2.Pathologic features of metastasis 3.Therapeutic ramifications Sir James Paget (1814-1899) British Surgeon/ Pathologist Paget s disease of bone Paget s disease of the
More informationDetermination Differentiation. determinated precursor specialized cell
Biology of Cancer -Developmental Biology: Determination and Differentiation -Cell Cycle Regulation -Tumor genes: Proto-Oncogenes, Tumor supressor genes -Tumor-Progression -Example for Tumor-Progression:
More informationBL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES. Overview and Mechanism of Action Dr.
BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES Overview and Mechanism of Action Dr. Leah Klapper, CSO 88 BL-8040: Novel CXCR4 Antagonist For Hematological Cancers Indications:
More informationIntroduction to Basic Oncology
Introduction to Basic Oncology Cancer Cell AHS 102 Med Term Dr. Susie Turner 1/3/13 General Oncology Study of Tumors Neoplasms/Tumors Abnormal growth of new tissue Are either; Benign or Malignant Onc/o
More informationCancer. Questions about cancer. What is cancer? What causes unregulated cell growth? What regulates cell growth? What causes DNA damage?
Questions about cancer What is cancer? Cancer Gil McVean, Department of Statistics, Oxford What causes unregulated cell growth? What regulates cell growth? What causes DNA damage? What are the steps in
More informationCELL CYCLE REGULATION AND CANCER. Cellular Reproduction II
CELL CYCLE REGULATION AND CANCER Cellular Reproduction II THE CELL CYCLE Interphase G1- gap phase 1- cell grows and develops S- DNA synthesis phase- cell replicates each chromosome G2- gap phase 2- cell
More informationDevelopment of Carcinoma Pathways
The Construction of Genetic Pathway to Colorectal Cancer Moriah Wright, MD Clinical Fellow in Colorectal Surgery Creighton University School of Medicine Management of Colon and Diseases February 23, 2019
More informationDisorders of Cell Growth & Neoplasia. Lecture 4 Molecular basis of cancer
General Pathology VPM 152 Disorders of Cell Growth & Neoplasia Lecture 4 Molecular basis of cancer Enrique Aburto Apr 2010 Skin tumor in a 10-year-old Rottweiler. Considering the external appearance and
More informationCHAPTER VII CONCLUDING REMARKS AND FUTURE DIRECTION. Androgen deprivation therapy is the most used treatment of de novo or recurrent
CHAPTER VII CONCLUDING REMARKS AND FUTURE DIRECTION Stathmin in Prostate Cancer Development and Progression Androgen deprivation therapy is the most used treatment of de novo or recurrent metastatic PCa.
More informationFunctional Limitations
Regulation of the Cell Cycle Chapter 12 Pg. 228 245 Functional Limitations Various factors determine whether and when a cell divides. Two functional limitations for cell size limit growth or influence
More informationLecture 8 Neoplasia II. Dr. Nabila Hamdi MD, PhD
Lecture 8 Neoplasia II Dr. Nabila Hamdi MD, PhD ILOs Understand the definition of neoplasia. List the classification of neoplasia. Describe the general characters of benign tumors. Understand the nomenclature
More information-The cell s hereditary endowment of DNA -Usually packaged into chromosomes for manageability
Binary Fission-Bacterial Cell Division -Asexual reproduction of prokaryotes -No mitosis -Circular DNA and organelles replicate, the copies migrate to opposite sides of the elongating cell, and the cell
More informationCell cycle, signaling to cell cycle, and molecular basis of oncogenesis
Cell cycle, signaling to cell cycle, and molecular basis of oncogenesis MUDr. Jiří Vachtenheim, CSc. CELL CYCLE - SUMMARY Basic terminology: Cyclins conserved proteins with homologous regions; their cellular
More informationCancer and Gene Alterations - 1
Cancer and Gene Alterations - 1 Cancer and Gene Alteration As we know, cancer is a disease of unregulated cell growth. Although we looked at some of the features of cancer when we discussed mitosis checkpoints,
More informationBCHM3972 Human Molecular Cell Biology (Advanced) 2013 Course University of Sydney
BCHM3972 Human Molecular Cell Biology (Advanced) 2013 Course University of Sydney Page 2: Immune Mechanisms & Molecular Biology of Host Defence (Prof Campbell) Page 45: Infection and Implications for Cell
More informationNeoplasia 18 lecture 8. Dr Heyam Awad MD, FRCPath
Neoplasia 18 lecture 8 Dr Heyam Awad MD, FRCPath ILOS 1. understand the angiogenic switch in tumors and factors that stimulate and inhibit angiogenesis. 2. list the steps important for tumor metastasis
More informationQuestion #1 Controls on cell growth and division turned on and off
Lesson Overview 10.3 Regulating the Cell Cycle Question #1 Controls on cell growth and division turned on and off When cells are grown in the laboratory, most cells will divide until they come into contact
More informationInflammatory Cells and Metastasis
Inflammatory Cells and Metastasis Experimentelle Krebsforschung SS 07 Gerhard Christofori Institute of Biochemistry and Genetics Department of Clinical-Biological Sciences Center of Biomedicine University
More informationChapter 9, Part 1: Biology of Cancer and Tumor Spread
PATHOPHYSIOLOGY Name Chapter 9, Part 1: Biology of Cancer and Tumor Spread I. Cancer Characteristics and Terminology Neoplasm new growth, involves the overgrowth of tissue to form a neoplastic mass (tumor).
More informationAP: CELL CYCLE REGULATION
AP: CELL CYCLE REGULATION CELL CYCLE 2 crucial factors for normal growth: Timing and rate of cell division Cell division frequency depends on cell type: skin cells: frequently Liver cells: can divide when
More information- is a common disease - 1 person in 3 can expect to contract cancer at some stage in their life -1 person in 5 can expect to die from it
MBB157 Dr D Mangnall The Molecular Basis of Disease CANCER Lecture 1 One of the simpler (and better) definitions of cancer comes from the American Cancer Society, who define cancer as; 'Cancer is a group
More informationCancer and Oncogenes Bioscience in the 21 st Century. Linda Lowe-Krentz October 11, 2013
Cancer and Oncogenes Bioscience in the 21 st Century Linda Lowe-Krentz October 11, 2013 Just a Few Numbers Becoming Cancer Genetic Defects Drugs Our friends and family 200 180 160 140 120 100 80 60 40
More informationAberrant cell Growth. Younas Masih New Life College of Nursing Karachi. 3/4/2016 Younas Masih ( NLCON)
Aberrant cell Growth Younas Masih New Life College of Nursing Karachi 1 Objectives By the end of this session the learners will be able to, Define the characteristics of the normal cell Describe the characteristics
More informationNegative Regulation of c-myc Oncogenic Activity Through the Tumor Suppressor PP2A-B56α
Negative Regulation of c-myc Oncogenic Activity Through the Tumor Suppressor PP2A-B56α Mahnaz Janghorban, PhD Dr. Rosalie Sears lab 2/8/2015 Zanjan University Content 1. Background (keywords: c-myc, PP2A,
More informationMolecular Biology of Cancer. Code: ECTS Credits: 6. Degree Type Year Semester
2018/2019 Molecular Biology of Cancer Code: 100863 ECTS Credits: 6 Degree Type Year Semester 2500252 Biochemistry OT 4 0 Contact Name: Carles Arús Caralto Email: Carles.Arus@uab.cat Other comments on languages
More informationHuman Lung Cancer Pathology and Cellular Biology Mouse Lung Tumor Workshop
Human Lung Cancer Pathology and Cellular Biology Mouse Lung Tumor Workshop Jan 7 th and 8 th, 2014 Brigitte Gomperts, MD University of California, Los Angeles Lung Structure and Function Airway Epithelial
More informationIntroduction to Cancer Biology
Introduction to Cancer Biology Robin Hesketh Multiple choice questions (choose the one correct answer from the five choices) Which ONE of the following is a tumour suppressor? a. AKT b. APC c. BCL2 d.
More informationNeoplasia 2018 lecture 4. Dr Heyam Awad MD, FRCPath
Neoplasia 2018 lecture 4 Dr Heyam Awad MD, FRCPath ILOS To understand the concept of the hallmarks of cancer and that they are phenotypic changes needed in all cancer cells. To list the tumor enablers
More informationDisorders of Cell Growth & Neoplasia
General Pathology VPM 152 Disorders of Cell Growth & Neoplasia Lecture 3 Rate of growth, local invasion, and metastasis. Molecular basis of cancer (normal cell-cycle and cellular proliferation). Enrique
More informationRegarding techniques of proteomics, there is:
Molecular الحلقة biology 14 واألخيرة To put you back in the context; the discussion was about Trancriptomics (the study of transcription). The following topic will be PROTEOMICS, which is the study of
More informationRAS Genes. The ras superfamily of genes encodes small GTP binding proteins that are responsible for the regulation of many cellular processes.
۱ RAS Genes The ras superfamily of genes encodes small GTP binding proteins that are responsible for the regulation of many cellular processes. Oncogenic ras genes in human cells include H ras, N ras,
More informationBreast Cancer and Biotechnology Jacquie L. Bay, Jo K. Perry and Peter E. Lobie
LENScience Senior Biology Seminar Series Breast Cancer and Biotechnology Jacquie L. Bay, Jo K. Perry and Peter E. Lobie Breast Cancer Each year in New Zealand, approximately 2,400 women and 20 men are
More informationCancer. October is National Breast Cancer Awareness Month
Cancer October is National Breast Cancer Awareness Month Objectives 1: Gene regulation Explain how cells in all the different parts of your body develop such different characteristics and functions. Contrast
More informationCANCER IMMUNOPATHOLOGY. Eryati Darwin Faculty of Medicine Andalas University
CANCER IMMUNOPATHOLOGY Eryati Darwin Faculty of Medicine Andalas University Padang 18 Mei 2013 INTRODUCTION Tumor: cells that continue to replicate, fail to differentiate into specialized cells, and become
More informationControl of Cell Cycle. Unit 2 Part f III
Control of Cell Cycle Unit 2 Part f III How often do cells divide and why? The timing and rate of cell division in different parts of the plant or animals are crucial to normal growth, development and
More informationMolecular Biology of Cancer. Code: ECTS Credits: 6. Degree Type Year Semester
2017/2018 Molecular Biology of Cancer Code: 100863 ECTS Credits: 6 Degree Type Year Semester 2500252 Biochemistry OT 4 0 Contact Name: Carles Arús Caralto Email: Carles.Arus@uab.cat Other comments on languages
More informationCell Death and Cancer. SNC 2D Ms. Papaiconomou
Cell Death and Cancer SNC 2D Ms. Papaiconomou How do cells die? Necrosis Death due to unexpected and accidental cell damage. This is an unregulated cell death. Causes: toxins, radiation, trauma, lack of
More informationNew Developments in the Treatment of Colorectal Cancer. Jonathan Loree, MD, MS, FRCPC Department of Medical Oncology BC Cancer Vancouver Centre
New Developments in the Treatment of Colorectal Cancer Jonathan Loree, MD, MS, FRCPC Department of Medical Oncology BC Cancer Vancouver Centre Personalized Medicine Currently already part of oncology:
More informationCrosstalk between Adiponectin and IGF-IR in breast cancer. Prof. Young Jin Suh Department of Surgery The Catholic University of Korea
Crosstalk between Adiponectin and IGF-IR in breast cancer Prof. Young Jin Suh Department of Surgery The Catholic University of Korea Obesity Chronic, multifactorial disorder Hypertrophy and hyperplasia
More informationDr Rodney Itaki Lecturer Anatomical Pathology Discipline. University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology
Neoplasia Dr Rodney Itaki Lecturer Anatomical Pathology Discipline University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology General Considerations Overview: Neoplasia uncontrolled,
More informationEnzyme-coupled Receptors. Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors
Enzyme-coupled Receptors Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors Cell-surface receptors allow a flow of ions across the plasma
More information2015 AP Biology Unit #4 Quiz 1 Cell Communication, Cancer and The Cell Cycle Week of November
Name: Class: Date: 2015 AP Biology Unit #4 Quiz 1 Cell Communication, Cancer and The Cell Cycle Week of 16-20 November Multiple Choice Identify the choice that best completes the statement or answers the
More informationOBJECTIVES. 1. List the major hallmarks of cancer. 2. Relate specific genes/proteins to individual hallmarks
OBJECTIVES 1. List the major hallmarks of cancer 2. Relate specific genes/proteins to individual hallmarks 3. Explain how hallmarks of cancer lead to cancer development Case Study 60 year old female Previously
More informationCancer genetics
Cancer genetics General information about tumorogenesis. Cancer induced by viruses. The role of somatic mutations in cancer production. Oncogenes and Tumor Suppressor Genes (TSG). Hereditary cancer. 1
More informationPhospho-AKT Sampler Kit
Phospho-AKT Sampler Kit E 0 5 1 0 0 3 Kits Includes Cat. Quantity Application Reactivity Source Akt (Ab-473) Antibody E021054-1 50μg/50μl IHC, WB Human, Mouse, Rat Rabbit Akt (Phospho-Ser473) Antibody
More informationGeneral Pathology VPM 152. Disorders of Cell Growth & Neoplasia. Lecture 4 Molecular basis of cancer
General Pathology VPM 152 Disorders of Cell Growth & Neoplasia Lecture 4 Molecular basis of cancer Enrique Aburto http://people.upei.ca/eaburto Winter 2015 Molecular Basis of Cancer Fundamental principles
More informationWhat causes cancer? Physical factors (radiation, ionization) Chemical factors (carcinogens) Biological factors (virus, bacteria, parasite)
Oncogenes What causes cancer? Chemical factors (carcinogens) Physical factors (radiation, ionization) Biological factors (virus, bacteria, parasite) DNA Mutation or damage Oncogenes Tumor suppressor genes
More informationPrinciples of Biology
Principles of Biology contents 55 Cancer The Genetic Basis of Cancers Chances are that you know someone who battled cancer, because one in every two men and one in every three women will develop cancer.
More informationTumor Associated Macrophages as a Novel Target for Cancer Therapy
Tumor mass Tumor Associated Macrophage Tumor Associated Macrophages as a Novel Target for Cancer Therapy This booklet contains forward-looking statements that are based on Amgen s current expectations
More informationPATHOBIOLOGY OF NEOPLASIA
PATHOBIOLOGY OF NEOPLASIA Department of Pathology Gadjah Mada University School of Medicine dr. Harijadi Blok Biomedis, 6 Maret 2009 [12] 3/17/2009 1 The pathobiology of neoplasia Normal cells Malignant
More informationOverview of the core ideas in cancer research
Overview of the core ideas in cancer research Paul Edwards Cancer Research UK Cambridge Institute and Department of Pathology, University of Cambridge This lecture Overview of the ideas that provide the
More informationBackgrounder. 1. What are targeted therapies? 2. How do targeted therapies work?
Backgrounder TARGETED THERAPIES FOR CANCER 1. What are targeted therapies? 2. How do targeted therapies work? 3. What are some of the different types of targeted therapy? 4. What are the potential benefits
More informationCYTOKINE RECEPTORS AND SIGNAL TRANSDUCTION
CYTOKINE RECEPTORS AND SIGNAL TRANSDUCTION What is Cytokine? Secreted popypeptide (protein) involved in cell-to-cell signaling. Acts in paracrine or autocrine fashion through specific cellular receptors.
More informationFrontiers in Cancer Therapy. John Glod, M.D., Ph.D.
Frontiers in Cancer Therapy John Glod, M.D., Ph.D. September 15, 2017 Objectives The Past: Alkylating agents The Present: Tyrosine Kinase Inhibitors The Future: Gene Expression, Metabolic cancers, CAR
More informationPancreatic intraepithelial
Pancreatic intraepithelial neoplasia (PanIN) Markéta Hermanová St. Anne s University Hospital Brno Faculty of Medicine, Masaryk University Precursor lesions of invasive pancreatic cancer Pancreatic intraepithelial
More informationMany Forms of Cell-Cell Communication Regulate Tissue Function and Phenotype Physiological Functions of Gap Junctions Homeostasis buffering/sharing of ions, nutrients, and water Metabolic support nutrient
More informationnumber Done by Corrected by Doctor Maha Shomaf
number 21 Done by Ahmad Rawajbeh Corrected by Omar Sami Doctor Maha Shomaf Ability to Invade and Metastasize The metastatic cascade can be subdivided into two phases: 1-invasion of ECM and vascular dissemination:
More informationKEY CONCEPT QUESTIONS IN SIGNAL TRANSDUCTION
Signal Transduction - Part 2 Key Concepts - Receptor tyrosine kinases control cell metabolism and proliferation Growth factor signaling through Ras Mutated cell signaling genes in cancer cells are called
More informationBiochemistry of Cancer and Tumor Markers
Biochemistry of Cancer and Tumor Markers The term cancer applies to a group of diseases in which cells grow abnormally and form a malignant tumor. It is a long term multistage genetic process. The first
More informationBreast Cancer and Biotechnology Jacquie Bay, Jo Perry, Michal Denny and Peter Lobie
LENScience Senior Biology Seminar Series Breast Cancer and Biotechnology Jacquie Bay, Jo Perry, Michal Denny and Peter Lobie Breast Cancer Each year in New Zealand, approximately 2,400 women and 20 men
More informationIn vitro scratch assay: method for analysis of cell migration in vitro labeled fluorodeoxyglucose (FDG)
In vitro scratch assay: method for analysis of cell migration in vitro labeled fluorodeoxyglucose (FDG) 1 Dr Saeb Aliwaini 13/11/2015 Migration in vivo Primary tumors are responsible for only about 10%
More informationp53 and Apoptosis: Master Guardian and Executioner Part 2
p53 and Apoptosis: Master Guardian and Executioner Part 2 p14arf in human cells is a antagonist of Mdm2. The expression of ARF causes a rapid increase in p53 levels, so what would you suggest?.. The enemy
More informationChristian Frezza MRC Cancer Unit
Christian Frezza MRC Cancer Unit What is cancer? What is cancer? Douglas Hanahan, Robert A. Weinberg; The Hallmarks of Cancer Cell, Volume 100, Issue 1, 7 January 2000, Pages 57 70 Cancer cells need energy
More informationLAPATINIB-Resistance to small Molecule ErbB2 Tyrosine Kinase Inhibitor (TKI)
LAPATINIB-Resistance to small Molecule ErbB2 Tyrosine Kinase Inhibitor (TKI) Prim Mr Sc Dr Suzana Vasović Institute for oncology and radiology of Serbia UMOS, X Conference, 16.05.2015 Belgrade How do we
More informationCellular Reproduction, Part 2: Meiosis Lecture 10 Fall 2008
Mitosis & 1 Cellular Reproduction, Part 2: Lecture 10 Fall 2008 Mitosis Form of cell division that leads to identical daughter cells with the full complement of DNA Occurs in somatic cells Cells of body
More informationI TESSUTI: Dott.ssa Liliana Belgioia Università degli Studi di Genova
I TESSUTI: 1. Repair, Radiosensitivity, Recruitment, Repopulation, Reoxygenation 2. Acute and chronic hypoxia 3. Tissue microenvironment and tissue organization Dott.ssa Liliana Belgioia Università degli
More informationMolecular and Cell Biology of Cancer. Code: ECTS Credits: 6. Degree Type Year Semester Biomedical Sciences OT 4 0
2018/2019 Molecular and Cell Biology of Cancer Code: 101897 ECTS Credits: 6 Degree Type Year Semester 2501230 Biomedical Sciences OT 4 0 Contact Name: Carles Arús Caralto Email: Carles.Arus@uab.cat Other
More informationA class of genes that normally suppress cell proliferation. p53 and Rb..ect. suppressor gene products can release cells. hyperproliferation.
Tumor Suppressor Genes A class of genes that normally suppress cell proliferation. p53 and Rb..ect Mutations that inactivate the tumor suppressor gene products can release cells from growth suppression
More informationChapter 12 The Cell Cycle
Chapter 12 The Cell Cycle Objectives Describe how cell reproduction contributes to repair and growth. Compare and contrast prokaryotic and eukaryotic cell division. Compare and contrast asexual and sexual
More informationSeeds and soil theory by Stephen Paget at the end of the XIX century.
Seeds and soil theory by Stephen Paget at the end of the XIX century. In The Distribution Of Secondary Growths In Cancer Of The Breast Paget presents and analyzes 735 fatal cases of breast cancer, complete
More informationEGFR Antibody. Necitumumab, LY , IMC-11F8. Drug Discovery Platform: Cancer Cell Signaling
EGFR Antibody Necitumumab, LY3012211, IMC-11F8 Derived from Yarden Y and Shilo BZ 1 ; Schneider MR and Wolf E. 2 Drug Discovery Platform: Cancer Cell Signaling A Single-Arm, Multicenter, Open-Label, Phase
More informationTOPICS. Primary Radiation Therapy. Targeted Therapy in Oncology. Principles of Radiation Therapy. Principles of Radiation Therapy
Peter B. Schiff, M.D., Ph.D. Department of Radiation Oncology Columbia University College of Physicians & Surgeons May 4, 2007 Targeted Therapy in Oncology Surgical Oncology Minimal invasive techniques
More informationA holistic approach to targeting breast cancer part II: Micronutrient synergy. Presented by: Dr. Neha Shanker DRRI
A holistic approach to targeting breast cancer part II: Micronutrient synergy Presented by: Dr. Neha Shanker DRRI Overview of the previous webinar In the last presentation we talked about: Increase in
More informationBreast Cancer Carcinogenesis: Mechanisms and Pathways in Hormone Receptor Positive Disease
Breast Cancer Carcinogenesis: Mechanisms and Pathways in Hormone Receptor Positive Disease 1 Nearly Two-Thirds of Metastatic Breast Cancers Express Hormone Receptors Breast cancer tumors are often classified
More information